13734-34-4

Basic information

• Product Name: N-(tert-Butoxycarbonyl)-L-phenylalanine
• Synonyms: n-[(1,1-dimethylethoxy)carbonyl]-l-phenylalanin;2-BOC-AMINO-3-PHENYL-PROPIONIC ACID;2-TERT-BUTOXYCARBONYLAMINO-3-PHENYL-PROPIONIC ACID;BOC-PHE-OH;BOC-PHENYLALANINE;BOC-PHE;BOC-L-PHE;BOC-L-PHENYLALANINE
• CAS NO: 13734-34-4
• Molecular Formula: C₁₄H₁₉NO₄
• Molecular Weight: 265.3
• EINECS: 237-305-5
• Product Categories: Protected Amino Acids;AMINOACIDS DERIVATIVES;Amino Acids;Phenylalanine [Phe, F];Boc-Amino Acids and Derivative;Amino Acids (N-Protected);Biochemistry;Boc-Amino Acids;Boc-Amino acid series;Amino Acids & Derivatives;Aromatics;Inhibitors
• Mol File: 13734-34-4.mol
• Article Data: 202

Chemical Properties

• Melting Point: 85-87 °C(lit.)
• Boiling Point: 408.52°C (rough estimate)
• Flash Point: 211.8 °C
• Appearance: White/Fine Crystalline Powder
• Density: 1.1356 (rough estimate)
• Vapor Pressure: 4.88E-08mmHg at 25°C
• Refractive Index: 24.5 ° (C=1, EtOH)
• Storage Temp.: -20°C
• Solubility: Soluble in methanol, dichloromethane, dimethylformamide and N-me
• PKA: 3.88±0.10(Predicted)
• BRN: 2219729
• CAS DataBase Reference: N-(tert-Butoxycarbonyl)-L-phenylalanine(CAS DataBase Reference)
• NIST Chemistry Reference: N-(tert-Butoxycarbonyl)-L-phenylalanine(13734-34-4)
• EPA Substance Registry System: N-(tert-Butoxycarbonyl)-L-phenylalanine(13734-34-4)

Safety Data

• Hazard Codes: Xn,Xi
• Statements: 36-22-36/37/38-20/21/22
• Safety Statements: 39-26-36-24/25
• WGK Germany: 3
• TSCA: Yes
• Hazardous Substances Data: 13734-34-4(Hazardous Substances Data)

Usage

Description

N-(tert-Butoxycarbonyl)-L-phenylalanine, also known as N-Boc-L-phenylalanine, is a derivative of the naturally occurring amino acid L-phenylalanine. It is characterized by the presence of a tert-butoxycarbonyl (Boc) protecting group, which is commonly used in organic synthesis to protect the amino group. This white fine crystalline powder is a valuable compound in various applications due to its unique chemical properties and reactivity.

Uses

1. Used in Enantioselective Hydrolysis of Amino Acid Esters:
N-(tert-Butoxycarbonyl)-L-phenylalanine is used as a chiral auxiliary in the enantioselective hydrolysis of amino acid esters. The presence of the Boc group enhances the selectivity of the reaction, allowing for the preferential formation of one enantiomer over the other. This is particularly important in the synthesis of pharmaceuticals and other chiral molecules, where the desired biological activity is often associated with a specific enantiomer.
2. Used as an Inhibitor of Gastric Acid Secretion:
N-(tert-Butoxycarbonyl)-L-phenylalanine is also utilized as an inhibitor of gastric acid secretion. By modulating the release of gastric acid, this compound can help in the treatment of conditions such as peptic ulcers, gastroesophageal reflux disease (GERD), and other acid-related disorders. The Boc group's protective nature plays a role in the compound's ability to regulate acid secretion, making it a valuable asset in the pharmaceutical industry.
3. Used in the Synthesis of Peptides and Proteins:
As a derivative of L-phenylalanine, N-(tert-Butoxycarbonyl)-L-phenylalanine can be incorporated into the synthesis of peptides and proteins. The Boc group serves as a temporary protecting group for the amino group during peptide synthesis, preventing unwanted side reactions and ensuring the correct formation of peptide bonds. Once the desired peptide or protein has been synthesized, the Boc group can be removed to reveal the free amino group, allowing for further modifications or the formation of additional peptide bonds.
4. Used in Research and Development:
N-(tert-Butoxycarbonyl)-L-phenylalanine is a valuable compound for researchers in the fields of organic chemistry, biochemistry, and pharmaceuticals. Its unique properties and reactivity make it an attractive candidate for the development of new synthetic methods, the study of enzyme mechanisms, and the design of novel bioactive molecules.

Preparation

Sodium hydroxide (4.4 g, 0.11 mol) was placed in a flask, and dissolved in water (110 mL). Phenylalanine (16.5 g, 0.1 mol) was added, the suspension was stirred until a solution was obtained, and then tert-butanol (75 mL) was added. Boc2O (22.3 g, 0.12 mol) was then added with stirring over a period of 1 h, keeping the mixture near 0 ℃. A white precipitate was produced, and at the end of the addition the pH had dropped to 7.5–8.5. The mixture was then carefully acidified by the slow, continuous addition of saturated citric acid to give the product N-tert-butoxycarbonyl-L-phenylalanine (21.5 g, 81%); mp 85℃; [a]21D = t25:5 (c = 1, ethanol).

InChI:InChI=1/C14H19NO4/c1-14(2,3)19-13(18)15-11(12(16)17)9-10-7-5-4-6-8-10/h4-8,11H,9H2,1-3H3,(H,15,18)(H,16,17)/p-1/t11-/m0/s1

Synthetic route

L-phenylalanine (63-91-2) + di-tert-butyl dicarbonate (24424-99-5) → N-tert-butoxycarbonyl-L-phenylalanine (13734-34-4)

Conditions	Yield
With sodium hydroxide In 1,4-dioxane at 0 - 20℃; for 3.5h;	100%
Stage #1: L-phenylalanine With sodium hydroxide In 1,4-dioxane; water at 0℃; for 0.25h; Stage #2: di-tert-butyl dicarbonate In 1,4-dioxane; water at 0 - 20℃;	100%
With sodium hydrogencarbonate; sodium hydroxide In 1,4-dioxane; water at 20℃; for 23h; Cooling with ice; Inert atmosphere;	100%

L-phenylalanine (63-91-2) + 2-t-butoxycarbonyloxy-3,6-diisopropylpyrazine (104272-92-6) → N-tert-butoxycarbonyl-L-phenylalanine (13734-34-4)

Conditions	Yield
With triethylamine In water; acetonitrile for 24h; Ambient temperature;	100%

2-tert-butoxycarbonylamino-3-phenylpropionic acid allyl ester (160788-63-6) → N-tert-butoxycarbonyl-L-phenylalanine (13734-34-4)

Conditions	Yield
With pyrrolidine; resin-plug bound Pd In tetrahydrofuran for 24h; Heating;	100%
With formic acid; triethylamine In acetonitrile at 80℃; for 4h; Inert atmosphere;	82%

(S)-2-tert-butoxycarbonylamino-3-phenyl-propionic acid methyl ester (51987-73-6) → N-tert-butoxycarbonyl-L-phenylalanine (13734-34-4)

Conditions	Yield
Stage #1: (S)-2-tert-butoxycarbonylamino-3-phenyl-propionic acid methyl ester With dimethylsulfoxonium methylide In tetrahydrofuran at 20℃; for 0.333333h; Inert atmosphere; Stage #2: With potassium hydrogensulfate; water In ethyl acetate pH=3; Inert atmosphere;	99%
Stage #1: (S)-2-tert-butoxycarbonylamino-3-phenyl-propionic acid methyl ester With lithium aluminium tetrahydride In tetrahydrofuran at 0℃; for 1h; Stage #2: With sodium hydroxide; water In tetrahydrofuran	98%
With sodium hydroxide In methanol

C20H31NO4S2 → N-tert-butoxycarbonyl-L-phenylalanine (13734-34-4)

Conditions	Yield
With 1,8-diazabicyclo[5.4.0]undec-7-ene; 2-hydroxyethanethiol at 20 - 25℃; for 0.166667h; Reagent/catalyst; Time;	99%

(S)-N-tert-butoxycarbonyl-2-amino-3-phenylpropanol (66605-57-0) → N-tert-butoxycarbonyl-L-phenylalanine (13734-34-4)

Conditions	Yield
With 2,2,6,6-tetramethyl-piperidine-N-oxyl; trichloroisocyanuric acid; sodium hydrogencarbonate; sodium bromide In water; acetone at 20℃; for 6h;	98%
With dipyridinium dichromate In N,N-dimethyl-formamide for 24h;	81%
Stage #1: (S)-N-tert-butoxycarbonyl-2-amino-3-phenylpropanol With Dess-Martin periodane In dichloromethane at 20℃; for 1.5h; Stage #2: With sodium chlorite; sodium dihydrogenphosphate; 2-methyl-but-2-ene In tetrahydrofuran; water; tert-butyl alcohol for 1.5h;

(S)-(1,1-dioxido-4-oxo-3-phenyl-4H-thiochromen-2-yl)methyl 2-((tert-butoxycarbonyl)amino)-3-phenylpropanoate → C16H10O3S (1033736-87-6) + N-tert-butoxycarbonyl-L-phenylalanine (13734-34-4)

Conditions	Yield
In chloroform-d1 for 0.233333h; Solvent; Photolysis; Inert atmosphere;	A n/a B 98%

{(R)-1-[((1S,2S)-2-Hydroxy-1-methyl-2-phenyl-ethyl)-methyl-carbamoyl]-2-phenyl-ethyl}-carbamic acid tert-butyl ester (185509-03-9) → N-tert-butoxycarbonyl-L-phenylalanine (13734-34-4) + Boc-D-Phe-OH (18942-49-9)

Conditions	Yield
With tetra(n-butyl)ammonium hydroxide In water; tert-butyl alcohol for 2.5h; Heating; Yields of byproduct given. Title compound not separated from byproducts;	A n/a B 97%

L-phenylalanine (63-91-2) → N-tert-butoxycarbonyl-L-phenylalanine (13734-34-4)

Conditions	Yield
With triethylamine In water; N,N-dimethyl-formamide for 12h; Ambient temperature;	96%

tert-butyl pyridin-2-yl carbonate (89985-91-1) + L-phenylalanine, dicyclohexylammonium salt → 2-hydroxypyridin (142-08-5) + N-tert-butoxycarbonyl-L-phenylalanine (13734-34-4)

Conditions	Yield
With triethylamine In water; N,N-dimethyl-formamide for 12h; Ambient temperature;	A n/a B 96%

L-phenylalanine (63-91-2) + 2-(tert-Butoxycarbonyloxyimino)-2-phenylacetonitrile (58632-95-4) → N-tert-butoxycarbonyl-L-phenylalanine (13734-34-4)

Conditions	Yield
With triethylamine In 1,4-dioxane; water for 3h;	95%
With triethylamine In 1,4-dioxane; water for 4h; Ambient temperature;
In acetonitrile at 25℃; for 12h;

L-phenylalanine (63-91-2) + tert-butyl 1H-benzo[d][1,2,3]triazole-1-carboxylate (130384-98-4) → N-tert-butoxycarbonyl-L-phenylalanine (13734-34-4)

Conditions	Yield
With sodium hydroxide In 1,4-dioxane for 24h; Ambient temperature;	95%

L-phenylalanine (63-91-2) + tert-butyl (2,4-dioxo-3-azaspiro[5,5]undecan-3-yl) carbonate → N-tert-butoxycarbonyl-L-phenylalanine (13734-34-4)

Conditions	Yield
With sodium carbonate In water; acetone at 25℃; for 9h; Temperature;	95%

L-phenylalanine (63-91-2) + tert-butyl 2-oxo-1,3-oxazole-3(2H)-carboxylate (75844-68-7) → N-tert-butoxycarbonyl-L-phenylalanine (13734-34-4)

Conditions	Yield
With dmap In water; acetone Ambient temperature;	93%
With dmap In 1,4-dioxane; water for 15h; Ambient temperature;	93%

L-phenylalanine (63-91-2) + (N-hydroxy-5-norbornene-2,3-diformylimino)tert-butyl ester (64205-15-8) → N-tert-butoxycarbonyl-L-phenylalanine (13734-34-4)

Conditions	Yield
With tertiary amine In 1,4-dioxane; water for 3h;	91%

tert-butyldicarbonate (34619-03-9) + L-phenylalanine (63-91-2) → N-tert-butoxycarbonyl-L-phenylalanine (13734-34-4)

Conditions	Yield
With sodium hydroxide In water; tert-butyl alcohol for 13h; Inert atmosphere;	91%

N-(tert-butoxycarbonyl)-L-phenylalanine benzyl ester (66617-58-1) → N-tert-butoxycarbonyl-L-phenylalanine (13734-34-4)

Conditions	Yield
With formic acid; potassium hydroxide In ethanol at 70℃; for 1h;	91%

di-tert-butyl dicarbonate (24424-99-5) + L-phenylalanine hydrochloride (17585-69-2, 27172-85-6, 28069-46-7, 74496-49-4, 79541-99-4) → N-tert-butoxycarbonyl-L-phenylalanine (13734-34-4)

Conditions	Yield
With sodium hydrogencarbonate In ethanol for 3h; sonication;	90%

2-tert-butoxycarbonylamino-3-phenyl-propionic acid 2-(2,5-dimethyl-phenyl)-2-oxo-ethyl ester → 2,3-dihydro-6-methyl-1H-inden-1-one (24623-20-9) + N-tert-butoxycarbonyl-L-phenylalanine (13734-34-4)

Conditions	Yield
In benzene Disproportionation; UV-irradiation;	A n/a B 90%

O-(tert-butyl) S-(pyridin-2-yl)carbonothioate (105678-24-8) + L-phenylalanine, dicyclohexylammonium salt → 2-Mercaptopyridine (2637-34-5) + N-tert-butoxycarbonyl-L-phenylalanine (13734-34-4)

Conditions	Yield
With triethylamine In water; N,N-dimethyl-formamide for 16h; Ambient temperature;	A n/a B 89%

N-[(1,1-dimethylethoxy)carbonyl]-L-phenylalanine 1,1-dimethylethyl ester (116400-16-9) → N-tert-butoxycarbonyl-L-phenylalanine (13734-34-4)

Conditions	Yield
With water; iodine In acetonitrile for 5h; Heating;	89%
With KSF clay In acetonitrile for 4.5h; Heating;	87%
With cerium(III) chloride; sodium iodide In acetonitrile for 6h; Heating;	78%
With trifluoroacetic acid

N-Boc-L-phenylalanine (1-nosyl-5-nitroindol-3-yl)methyl ester → N-tert-butoxycarbonyl-L-phenylalanine (13734-34-4)

Conditions	Yield
Stage #1: N-Boc-L-phenylalanine (1-nosyl-5-nitroindol-3-yl)methyl ester With 2-(N,N-dimethylamino)ethylthiol hydrochloride; 1,8-diazabicyclo[5.4.0]undec-7-ene In acetonitrile at 20℃; for 0.25h; Inert atmosphere; Stage #2: With hydrogenchloride In diethyl ether; water; acetonitrile Inert atmosphere;	88%

L-phenylalanine (63-91-2) + dimethylsulfonium methylsulfate → N-tert-butoxycarbonyl-L-phenylalanine (13734-34-4)

Conditions	Yield
With triethylamine In water Ambient temperature;	84%

L-phenylalanine (63-91-2) + 2-(tert-Butoxycarbonyloxyimino)-2-phenylacetonitrile (58632-95-4) → 2-(hydroxyimino)-2-phenylacetonitrile (825-52-5) + N-tert-butoxycarbonyl-L-phenylalanine (13734-34-4)

Conditions	Yield
With triethylamine In 1,4-dioxane; water for 3h;	A n/a B 83%

L-phenylalanine (63-91-2) + 1,2,2,2-Tetrachloroethyl tert-Butyl Carbonate (98015-52-2) → N-tert-butoxycarbonyl-L-phenylalanine (13734-34-4)

Conditions	Yield
With triethylamine In 1,4-dioxane; water at 20℃; for 6h;	79%
With triethylamine In 1,4-dioxane; water at 20℃; for 5h;	79%

(S)-2-tert-Butoxycarbonylamino-3-phenyl-propionic acid 2-trimethylsilanyl-ethoxymethyl ester → N-tert-butoxycarbonyl-L-phenylalanine (13734-34-4)

Conditions	Yield
With magnesium bromide In dichloromethane for 2.5h; Ambient temperature; addition at -20 deg C, 0.5 h;	78%

L-phenylalanine (63-91-2) + 1-(t-butoxycarbonyl)-1,2,4-triazolo<4,3-a>pyridinium-3-olate (50739-44-1) → N-tert-butoxycarbonyl-L-phenylalanine (13734-34-4)

Conditions	Yield
With pyridine; sodium hydroxide In 1,4-dioxane for 4h; Ambient temperature;	77%

Boc-Phe-O-(F)TMSE (1174669-41-0) → N-tert-butoxycarbonyl-L-phenylalanine (13734-34-4)

Conditions	Yield
With (F)TBAF In tetrahydrofuran; N,N-dimethyl-formamide at 40℃; for 1h; Inert atmosphere; Microwave irradiation;	72%

Boc-Phe-NHNHPh (17790-88-4) → N-tert-butoxycarbonyl-L-phenylalanine (13734-34-4)

Conditions	Yield
With oxygen for 6h; tyrosinase, phosphate buffer pH 7;	65%
With phosphate buffer; oxygen; tyrosinase In water; acetonitrile at 20℃; for 6h; pH=7.0;	65%

L-phenylalanine (63-91-2) + N-tert-Butoxycarbonyl-N-trifluoromethylsulfonyl-4-trifluoromethylanilide (250296-58-3) → N-tert-butoxycarbonyl-L-phenylalanine (13734-34-4)

Conditions	Yield
With water; triethylamine In 1,4-dioxane at 20℃; for 24h; Acylation;	59%

methyl (2S)-2-amino-3-phenylpropanoate (2577-90-4) + N-tert-butoxycarbonyl-L-phenylalanine (13734-34-4) → (S)-methyl 2-((S)-2-(tert-butoxycarbonylamino)-3-phenylpropanamido)-3-phenylpropanoate (13122-89-9)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In various solvent(s) at 65℃; for 3h;	100%
With 6-chloro-3-((dimethylamino)(dimethyliminio)methyl)-1H-benzo[d][1,2,3]triazol-3-ium-1-olatehexafluorophosphate(V); N-ethyl-N,N-diisopropylamine In dichloromethane	98%
With 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride In Dichlorodifluoromethane; water at 20℃; for 3h;	96%

N-tert-butoxycarbonyl-L-phenylalanine (13734-34-4) + methyl iodide (74-88-4) → Boc-N-Me-Phe-OH (37553-65-4)

Conditions	Yield
With sodium hydride In N,N-dimethyl-formamide	100%
With 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone; sodium hydride In tetrahydrofuran at 0 - 20℃; for 18.5h;	100%
With sodium hydride In tetrahydrofuran at 20℃; for 18h;	100%

N-tert-butoxycarbonyl-L-phenylalanine (13734-34-4) + N,O-dimethylhydroxylamine*hydrochloride (6638-79-5) → Boc-Phe-OH N,O-dimethyl hydroxamate (87694-53-9)

Conditions	Yield
With benzotriazol-1-ol; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide; N-ethyl-N,N-diisopropylamine In acetonitrile Acylation;	100%
Stage #1: N-tert-butoxycarbonyl-L-phenylalanine With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 0℃; for 0.25h; Inert atmosphere; Stage #2: N,O-dimethylhydroxylamine*hydrochloride With 4-methyl-morpholine In dichloromethane at 0 - 25℃; for 14h; Inert atmosphere;	100%
Stage #1: N-tert-butoxycarbonyl-L-phenylalanine With 4-methyl-morpholine; isobutyl chloroformate In dichloromethane at 0℃; for 0.333333h; Stage #2: N,O-dimethylhydroxylamine*hydrochloride With triethylamine In dichloromethane for 1.25h;	100%

N-tert-butoxycarbonyl-L-phenylalanine (13734-34-4) + L-isoleucine tert-butyl ester hydrochloride (69320-89-4) → Boc-Phe-Ile-OtBu

Conditions	Yield
With 4-methyl-morpholine; (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate In N,N-dimethyl-formamide for 2h;	100%

N-tert-butoxycarbonyl-L-phenylalanine (13734-34-4) + (1S,2R)-1-amino-2-indanol (7480-35-5, 13286-59-4, 74165-73-4, 126456-43-7, 136030-00-7, 140632-19-5, 140632-20-8) → (S)-2-(tert-butoxycarbonylamino)-N-((1S,2R)-2-hydroxy-1-indanyl)-3-phenylpropanamide (140468-58-2)

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 1h;	100%
With 1-hydroxybenzotriazol-hydrate; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In N,N-dimethyl-formamide for 18h; Ambient temperature;	5.50 g
With benzotriazol-1-ol; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide; triethylamine In N,N-dimethyl-formamide for 18h; Ambient temperature;

N-tert-butoxycarbonyl-L-phenylalanine (13734-34-4) → (S)-2-[(tert-butoxycarbonyl)amino]-3-phenylpropionamide (88463-18-7)

Conditions	Yield
Stage #1: N-tert-butoxycarbonyl-L-phenylalanine With chloroformic acid ethyl ester; triethylamine In tetrahydrofuran at 0℃; for 0.5h; Stage #2: With ammonium chloride In tetrahydrofuran; water at 0℃; for 0.5h;	100%
Stage #1: N-tert-butoxycarbonyl-L-phenylalanine With 4-methyl-morpholine; isobutyl chloroformate In tetrahydrofuran at -20℃; Inert atmosphere; Stage #2: With ammonium hydroxide In tetrahydrofuran at -20 - 20℃;	98%
With ammonium bicarbonate; N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline In chloroform Ambient temperature;	91%

N-tert-butoxycarbonyl-L-phenylalanine (13734-34-4) → (S)-N-tert-butoxycarbonyl-2-amino-3-phenylpropanol (66605-57-0)

Conditions	Yield
Stage #1: N-tert-butoxycarbonyl-L-phenylalanine With 4-methyl-morpholine; isobutyl chloroformate In tetrahydrofuran at -15℃; for 0.25h; Stage #2: With sodium tetrahydroborate In tetrahydrofuran; water at -15℃; for 1h;	100%
With sodium tetrahydroborate; 2-(6-nitro-1-oxy-benzotriazol-3-yl)-1,1,3,3-Me4-uronium*PF6; N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 20℃; for 0.5h;	93%
Stage #1: N-tert-butoxycarbonyl-L-phenylalanine With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 0.5h; Stage #2: With sodium tetrahydroborate; water In tetrahydrofuran at 0℃; for 0.5h;	92%

N-tert-butoxycarbonyl-L-phenylalanine (13734-34-4) + tert-butyldimethylsilyl chloride (18162-48-6) → C20H33NO4Si (130529-77-0)

Conditions	Yield
With triethylamine In ethyl acetate at 0℃; for 30h;	100%

N-tert-butoxycarbonyl-L-phenylalanine (13734-34-4) + chloroacetonitrile (107-14-2) → (S)-cyanomethyl 2-((tert-butoxycarbonyl)amino)-3-phenylpropanoate (127357-85-1)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 20℃;	100%
With N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 20℃;	100%
With triethylamine for 2h; Ambient temperature;	89%

N-tert-butoxycarbonyl-L-phenylalanine (13734-34-4) + 1-amino-2-propene (107-11-9) → (S)-tert-butyl (1-(allylamino)-1-oxo-3-phenylpropan-2-yl)carbamate (120125-16-8)

Conditions	Yield
With 4-methyl-morpholine; isobutyl chloroformate In tetrahydrofuran at -25 - 20℃; for 2h;	100%
With triethylamine; isobutyl chloroformate In dichloromethane at 20℃; for 15h;	84%
With 4-methyl-morpholine; benzotriazol-1-ol; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide In N,N-dimethyl-formamide at 5℃;
With dmap; dicyclohexyl-carbodiimide In tetrahydrofuran

N-tert-butoxycarbonyl-L-phenylalanine (13734-34-4) + dibenzyl dicarbonate (31139-36-3) → N-(tert-butoxycarbonyl)-L-phenylalanine benzyl ester (66617-58-1)

Conditions	Yield
With dmap In tetrahydrofuran for 0.333333h;	100%

N-tert-butoxycarbonyl-L-phenylalanine (13734-34-4) + 3-aminodihydrothiophen-2(3H)-one hydrochloride (6038-19-3) → [(S)-1-(2-Oxo-tetrahydro-thiophen-3-ylcarbamoyl)-2-phenyl-ethyl]-carbamic acid tert-butyl ester (192310-93-3)

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In dichloromethane for 4h; Ambient temperature;	100%

N-tert-butoxycarbonyl-L-phenylalanine (13734-34-4) → (S)-tert-butyl (1-hydrazinyl-1-oxo-3-phenylpropan-2-yl)carbamate (30189-48-1)

Conditions	Yield
With pyridine; bis-(2-oxo-3-oxazolidinyl)phosphoryl chloride; hydrazine at 20℃; for 16h; Reagent/catalyst; Inert atmosphere;	100%
With hydrazine hydrate In methanol for 18h;	68%
(i) ClCO2Et, Et3N, THF, (ii) N2H4*H2O; Multistep reaction;

N-tert-butoxycarbonyl-L-phenylalanine (13734-34-4) + benzyl bromide (100-39-0) → N-(tert-butoxycarbonyl)-L-phenylalanine benzyl ester (66617-58-1)

Conditions	Yield
With potassium carbonate In acetonitrile at 0 - 20℃; for 24h; Further stages;	100%
With potassium carbonate In acetone Heating / reflux;	99%
With potassium carbonate In acetonitrile for 24h; Reflux;	93%

cycl-isopropylidene malonate (2033-24-1) + N-tert-butoxycarbonyl-L-phenylalanine (13734-34-4) → (S)-[1-benzyl-2-(2,2-dimethyl-4,6-dioxo-[1,3]dioxan-5-yl)-2-oxo-ethyl]-carbamic acid tert-butyl ester (109579-08-0)

Conditions	Yield
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 0 - 20℃; for 16h;	100%
With dmap; dicyclohexyl-carbodiimide In dichloromethane at 0℃; for 12h; Inert atmosphere;	95%
Stage #1: cycl-isopropylidene malonate; N-tert-butoxycarbonyl-L-phenylalanine With dmap In dichloromethane for 0.166667h; Cooling with ice; Stage #2: With dicyclohexyl-carbodiimide In dichloromethane for 10h; Cooling with ice;	77%

N-tert-butoxycarbonyl-L-phenylalanine (13734-34-4) + 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (3945-69-5) → 2-tert-butoxycarbonylamino-3-phenyl-propionic acid 4,6-dimethoxy-[1,3,5]triazin-2-yl ester (1025839-59-1)

Conditions	Yield
In 1,2-dimethoxyethane at 0℃; for 3h; Condensation;	100%

1-phenylmethylpiperazine (2759-28-6) + N-tert-butoxycarbonyl-L-phenylalanine (13734-34-4) → (S)-[1-benzyl-2-(4-benzyl-piperazin-1-yl)-2-oxo-ethyl]-carbamic acid tert-butyl ester (154812-31-4)

Conditions	Yield
Stage #1: N-tert-butoxycarbonyl-L-phenylalanine With O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate In dichloromethane at 20℃; for 1h; Inert atmosphere; Stage #2: 1-phenylmethylpiperazine In dichloromethane at 20℃;	100%
With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; for 8h;	91%
With diethyl cyanophosphonate; triethylamine In dichloromethane Condensation;

N-tert-butoxycarbonyl-L-phenylalanine (13734-34-4) + (3RS)-3-amino-1-cyclohexyl-carbonylmethyl-2,3-dihydro-5-ethyl-9-methyl-1H-1,4-benzodiazepin-2-one (205996-41-4) → (3RS)-1-cyclohexylcarbonylmethyl-3-[N-tert-butoxycarbonyl-(S)-phenylalanyl]amino-5-ethyl-2,3-dihydro-9-methyl-1H-1,4-benzodiazepin-2-one (205998-78-3)

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 20℃; Acylation;	100%

cycl-isopropylidene malonate (2033-24-1) + N-tert-butoxycarbonyl-L-phenylalanine (13734-34-4) → (2'S)-5-<(1-hydroxy-3-phenyl-2-t-butoxycarbonylamino)-propylidene>-2,2-dimethyl-1,3-dioxane-4,6-dione (112700-36-4, 112700-37-5)

Conditions	Yield
With dmap; dicyclohexyl-carbodiimide In dichloromethane at 0 - 20℃;	100%
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 0℃;
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 0 - 25℃; for 14h; Inert atmosphere;
With dmap; dicyclohexyl-carbodiimide In dichloromethane at 0 - 20℃;

methanol (67-56-1) + N-tert-butoxycarbonyl-L-phenylalanine (13734-34-4) → (S)-2-tert-butoxycarbonylamino-3-phenyl-propionic acid methyl ester (51987-73-6)

Conditions	Yield
With thionyl chloride at 0 - 20℃; for 24h;	100%
With 4-methyl-morpholine; 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride In water for 3h;	96%
With cyano-hydroxyimino-acetic acid 2,2-dimethyl-[1,3]dioxolan-4-ylmethyl ester; sodium hydrogencarbonate; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In water; acetonitrile	95%

N-tert-butoxycarbonyl-L-phenylalanine (13734-34-4) + cycloleucine methyl ester (78388-61-1) → BocPhe-cLeuOMe

Conditions	Yield
With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In various solvent(s) at 65℃; for 3h;	100%

N-tert-butoxycarbonyl-L-phenylalanine (13734-34-4) + o-SSEt-phenol (714229-46-6) → 2-tert-butoxycarbonylamino-3-phenyl-propionic acid 2-ethyldisulfanyl-phenyl ester (714229-47-7)

Conditions	Yield
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In tetrahydrofuran; dichloromethane at 20℃; for 18h;	100%

N-tert-butoxycarbonyl-L-phenylalanine (13734-34-4) + allyl bromide (106-95-6) → 2-tert-butoxycarbonylamino-3-phenylpropionic acid allyl ester (160788-63-6)

Conditions	Yield
With potassium hydrogencarbonate In N,N-dimethyl-formamide at 0 - 20℃; for 15h;	100%
With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 0 - 22℃; for 16h; Inert atmosphere;	99%
With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 0 - 20℃;	98%
With potassium hydrogencarbonate In N,N-dimethyl-formamide at 0 - 20℃; for 15h; Inert atmosphere;	92%
With tetrabutylammomium bromide; potassium carbonate In N,N-dimethyl-formamide at 0 - 20℃; Inert atmosphere;

N-tert-butoxycarbonyl-L-phenylalanine (13734-34-4) + 4,6-O-di(tert-butyl)silanediyl-D-glucal (191593-14-3) → 3-O-(N-tert-butoxycarbonyl-L-phenylalanyl)-4,6-O-di-tert-butylsilanediyl-D-glucal

Conditions	Yield
With dmap; dicyclohexyl-carbodiimide In dichloromethane	100%

N-tert-butoxycarbonyl-L-phenylalanine (13734-34-4) + Propargylamine (2450-71-7) → (S)-tert-butyl (1-oxo-3-phenyl-1-(prop-2-yn-1-ylamino)propan-2-yl)carbamate (461638-99-3)

Conditions	Yield
With benzotriazol-1-ol; dicyclohexyl-carbodiimide In dichloromethane for 2h; Inert atmosphere; Reflux;	100%
With benzotriazol-1-ol; diisopropyl-carbodiimide In dichloromethane at 0 - 20℃; for 16h; Inert atmosphere;	95%
With benzotriazol-1-ol; dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 12h; Inert atmosphere;	93%

5-{4-[2-amino-2-(1H-benzoimidazol-2-yl)-ethyl]-phenyl}-2-tert-butyl-1,1-dioxo-1λ6-isothiazolidin-3-one; compound with trifluoro-acetic acid + N-tert-butoxycarbonyl-L-phenylalanine (13734-34-4) → tert-butyl (1S)-2-[((1S)-1-(1H-benzimidazol-2-yl)-2-4-[(5S)-2-tert-butyl-1,1-dioxido-3-oxoisothiazolidin-5-yl]phenylethyl)amino]-1-benzyl-2-oxoethylcarbamate (918959-20-3)

Conditions	Yield
Stage #1: N-tert-butoxycarbonyl-L-phenylalanine With N-ethyl-N,N-diisopropylamine; HATU In 1-methyl-pyrrolidin-2-one for 0.0833333h; Stage #2: 5-{4-[2-amino-2-(1H-benzoimidazol-2-yl)-ethyl]-phenyl}-2-tert-butyl-1,1-dioxo-1λ6-isothiazolidin-3-one; compound with trifluoro-acetic acid With N-ethyl-N,N-diisopropylamine In 1-methyl-pyrrolidin-2-one; dimethyl sulfoxide at 20℃;	100%

N-tert-butoxycarbonyl-L-phenylalanine (13734-34-4) + Benzhydrylamine (91-00-9) → N-α-t-butoxycarbonyl-L-phenylalanine-N-benzhydrylamide (143553-18-8)

Conditions	Yield
With diethyl cyanophosphonate; N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 0 - 20℃; for 16h;	100%

Upstream product

• 1070-19-5 N-(tert-butyloxycarbonyl) azide 
• 63-91-2 L-phenylalanine 
• 13303-10-1 tert-Butyl 4-nitrophenyl carbonate 
• 24608-52-4 tert-butyl chloroformate 
• 105678-24-8 O-(tert-butyl) S-(pyridin-2-yl)carbonothioate 
• 116400-16-9 N-[(1,1-dimethylethoxy)carbonyl]-L-phenylalanine 1,1-dimethylethyl ester 
• 66605-57-0 (S)-N-tert-butoxycarbonyl-2-amino-3-phenylpropanol 
• 17790-88-4 Boc-Phe-NHNHPh 
• 335628-25-6 (4S,5R)-4-benzyl-3-tert-butoxycarbonyl-5-methoxy-2-oxazolidinone 
• 160788-63-6 2-tert-butoxycarbonylamino-3-phenylpropionic acid allyl ester 
• 691-64-5 di-tert-butyl oxalate 
• 4530-20-5 BOC-glycine 
• 75-65-0 tert-butyl alcohol 
• 181118-08-1 Boc-L-Phe-OGp 

Downstream Products

• 56414-89-2 L-phenylalanine N¹,N¹-(tetramethylene)amide 
• 78569-23-0 3-(N-t-butoxycarbonyl-L-phenylalanyl)-1,3-thiazolidine-2-thione 
• 83031-02-1 t-butoxycarbonyl-L-phenylalanine 4-picolyl ester 
• 97512-72-6 methyl (Z)-2-({(2S)-2-[(tert-butoxycarbonyl)amino]-3-phenylpropanoyl}-amino)-3-phenyl-2-propenoate 
• 87363-79-9 Boc-(L)-Ala-Δbut-OMe 
• 115572-87-7 (S)-2-tert-Butoxycarbonylamino-3-phenyl-propionic acid 2-thioxo-2H-pyridin-1-yl ester 
• 113378-38-4 N-carboxy Boc-Phe-ΔLeu anhydride 
• 3674-06-4 Boc-Phe-ONSu 
• 144090-39-1 1-((S)-2-tert-Butoxycarbonylamino-3-phenyl-propionyl)-1,2,3,6-tetrahydro-pyridine-2-carboxylic acid methyl ester 
• 137005-58-4 (S)-[1-benzyl-2-oxo-2-(4-phenyl-piperidin-1-yl)-ethyl]-carbamic acid tert-butyl ester 
• 134268-98-7 Boc-Phe-NH-c 
• 111895-79-5 H-Pro-His-Pro-Phe-His-Phe-Phe-ε Ahx-OH 
• 125049-29-8 C₃₀H₃₁BrN₂O₃ 
• 4522-04-7 ethyl N-{[(1,1-dimethylethyl)oxy]carbonyl}-L-phenylalaninate 

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