5854-78-4

Basic information

• Product Name: H-THR(TBU)-OTBU
• Synonyms: H-THR(TBU)-OTBU;O-TERT-BUTYL-L-THREONINE TERT-BUTYL ESTER;O-T-BUTYL-L-THREONINE T-BUTYL ESTER;THREONINE(TBU)-OTBU;Glu(OtBu)-OMe.HCl;O-TERT-BUTYL-L-THREONINET-BUTYLESTER;(2S,3R)-tert-Butyl 2-aMino-3-(tert-butoxy)butanoate;L-Thr(tBu)-OtBu
• CAS NO: 5854-78-4
• Molecular Formula: C₁₂H₂₅NO₃
• Molecular Weight: 231.33
• Mol File: 5854-78-4.mol
• Article Data: 6

Chemical Properties

• Melting Point: 74-75 °C
• Boiling Point: 70°C/0.8mmHg(lit.)
• Flash Point: 79.3 °C
• Appearance: /
• Density: 0.959 g/cm³
• Vapor Pressure: 0.00146mmHg at 25°C
• Refractive Index: 1.4320-1.4360
• Storage Temp.: -15°C
• PKA: 6.14±0.33(Predicted)
• CAS DataBase Reference: H-THR(TBU)-OTBU(CAS DataBase Reference)
• NIST Chemistry Reference: H-THR(TBU)-OTBU(5854-78-4)
• EPA Substance Registry System: H-THR(TBU)-OTBU(5854-78-4)

Safety Data

• Hazardous Substances Data: 5854-78-4(Hazardous Substances Data)

Usage

Description

H-THR(TBU)-OTBU, also known as O-tert-Butylthreonine tert-Butyl Ester, is a light yellowish liquid with unique chemical properties. It serves as a key intermediate in the synthesis of various chemical compounds with therapeutic activity, making it a valuable component in the pharmaceutical industry.

Uses

Used in Pharmaceutical Industry:
H-THR(TBU)-OTBU is used as a key intermediate for the synthesis of chemical compounds with therapeutic activity. Its role in creating compounds like N-[[[(1S)-1-[3-(2-Pyrazinyl)-1,2,4-oxadiazol-5-yl]-3-butyn-1-yl]amino]carbonyl]-L-threonine (P842605) highlights its importance in developing immune modulators.
Used in Immune Modulation:
H-THR(TBU)-OTBU is used as a building block in the development of immune modulators, specifically in the synthesis of P842605. These immune modulators play a crucial role in regulating the immune system and can be employed in the treatment of various immune-related disorders and conditions.

InChI:InChI=1/C12H25NO3/c1-8(15-11(2,3)4)9(13)10(14)16-12(5,6)7/h8-9H,13H2,1-7H3/t8-,9+/m1/s1

Synthetic route

L-threonine (72-19-5) + isobutene (115-11-7) → (2S,3R)-tert-butyl 2-amino-3-tert-butoxybutanoate (5854-78-4)

Conditions	Yield
Stage #1: L-threonine With trifluorormethanesulfonic acid In 1,2-dimethoxyethane at -10 - 5℃; Stage #2: isobutene In 1,2-dimethoxyethane at -15 - -10℃; for 48h; Reagent/catalyst; Solvent;	67.2%
Stage #1: L-threonine; isobutene With sulfuric acid In 1,2-dimethoxyethane at -5 - 5℃; for 24h; Stage #2: With ammonia In water at 0℃;

L-threonine (72-19-5) + tert-butyl methyl ether (1634-04-4) → (2S,3R)-tert-butyl 2-amino-3-tert-butoxybutanoate (5854-78-4)

Conditions	Yield
With sulfuric acid at 25℃; for 2h; Molecular sieve; chemoselective reaction;	30%

N-Carbobenzoxy-O-tert.-butyl-L-threonin-tert.-butylester (14437-51-5) → (2S,3R)-tert-butyl 2-amino-3-tert-butoxybutanoate (5854-78-4)

Conditions	Yield
With hydrogen; palladium In methanol
With hydrogen; palladium on activated charcoal In methanol
With hydrogen; palladium on activated charcoal In N,N-dimethyl-formamide
With hydrogen; palladium on activated charcoal In methanol for 2h; Ambient temperature;

N-benzyloxycarbonyl-L-treonine (19728-63-3) + isobutene (115-11-7) → (2S,3R)-tert-butyl 2-amino-3-tert-butoxybutanoate (5854-78-4)

Conditions	Yield
(i) H2SO4, CH2Cl2, (ii) H2, Pd-BaSO4, MeOH; Multistep reaction;
(i) H2SO4, (ii) (hydrogenolysis); Multistep reaction;
(i) H2SO4, CH2Cl2, (ii) H2, Pd-C, EtOH; Multistep reaction;

tert-butyl methyl ether (1634-04-4) + tert-butyl (2S,3R)-2-amino-3-hydroxybutanoate (17083-30-6, 66748-90-1, 67580-85-2, 150693-46-2, 150693-47-3) → (2S,3R)-tert-butyl 2-amino-3-tert-butoxybutanoate (5854-78-4)

Conditions	Yield
With ZSM-5 supported silicotungstic acid at 70℃; Temperature;

(2S,3R)-tert-butyl 2-amino-3-tert-butoxybutanoate (5854-78-4) + 2-Azidoethyl α-D-galactopyranosiduronic acid (158000-10-3) → N-(2-Azidoethyl α-D-galactopyranosiduronoyl)-O-(tert-butyl)-L-threonine tert-butyl ester

Conditions	Yield
With N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline In N,N-dimethyl-formamide at 20℃; for 72h;	100%

C12H15NO7 (1147133-24-1) + (2S,3R)-tert-butyl 2-amino-3-tert-butoxybutanoate (5854-78-4) → C24H38N2O9 (1147134-79-9)

Conditions	Yield
With 2,6-dimethylpyridine; 1-hydroxy-7-aza-benzotriazole; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide for 24h;	100%

(2S,3R)-tert-butyl 2-amino-3-tert-butoxybutanoate (5854-78-4) + N-Fmoc L-Phe (35661-40-6) → t-butyl-N-fluoren-9-ylmethyloxycarbonyl-L-phenylalanyl-O-t-butyl-L-threonine (87720-56-7)

Conditions	Yield
With dicyclohexyl-carbodiimide In dichloromethane; N,N-dimethyl-formamide at 20℃; for 18h;	99%

(2S,3R)-tert-butyl 2-amino-3-tert-butoxybutanoate (5854-78-4) + 3-[(tert-butoxycarbonyl)amino]-3-methylbutanoic acid (129765-95-3) → Boc-β-HoAib-L-Thr(t-Bu)-O-t-Bu

Conditions	Yield
With pentamethoxy tantalum; 1-(Trimethylsilyl)imidazole In neat (no solvent) at 50℃; for 48h; Inert atmosphere; Sealed tube;	99%

L-N-Boc-Ala (15761-38-3) + (2S,3R)-tert-butyl 2-amino-3-tert-butoxybutanoate (5854-78-4) → Boc-L-Ala-L-Thr(t-Bu)-O-t-Bu

Conditions	Yield
With pentamethoxy tantalum; 1-(Trimethylsilyl)imidazole In neat (no solvent) at 50℃; for 72h; Inert atmosphere; Sealed tube;	98%

(2S,3R)-tert-butyl 2-amino-3-tert-butoxybutanoate (5854-78-4) + (2S,3S,4S,5R,6R)-6-[(2R,3R,4R,5S,6S)-2-(2-Acryloylamino-ethoxy)-3,5-dihydroxy-6-methyl-tetrahydro-pyran-4-yloxy]-3,4,5-trihydroxy-tetrahydro-pyran-2-carboxylic acid (127879-03-2) → (2S,3R)-2-({(2S,3S,4S,5R,6R)-6-[(2R,3R,4R,5S,6S)-2-(2-Acryloylamino-ethoxy)-3,5-dihydroxy-6-methyl-tetrahydro-pyran-4-yloxy]-3,4,5-trihydroxy-tetrahydro-pyran-2-carbonyl}-amino)-3-tert-butoxy-butyric acid tert-butyl ester (136632-51-4)

Conditions	Yield
With N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline In N,N-dimethyl-formamide at 20℃;	95%

(2S,3R)-tert-butyl 2-amino-3-tert-butoxybutanoate (5854-78-4) + 2-(9H-fluoren-9-ylmethoxycarbonylamino)-3-methyl-thiobutyric acid S-(2-formyl-4-nitro-phenyl) ester (557095-50-8) → Fmoc-Val-Thr(t-Bu)-O-Bu-t (557095-67-7)

Conditions	Yield
With N-methylmaleimide; N-ethyl-N,N-diisopropylamine In 1,4-dioxane; water; N,N-dimethyl-formamide at 20℃; for 2.5h;	95%

(2S,3R)-tert-butyl 2-amino-3-tert-butoxybutanoate (5854-78-4) + 2-azidoethyl 3-O-(α-L-rhamnopyranosyl)-β-D-glucopyranosiduronic acid (136632-48-9) → (2S,3R)-2-{[(2S,3S,4S,5R,6R)-6-(2-Azido-ethoxy)-3,5-dihydroxy-4-((2S,3R,4R,5R,6S)-3,4,5-trihydroxy-6-methyl-tetrahydro-pyran-2-yloxy)-tetrahydro-pyran-2-carbonyl]-amino}-3-tert-butoxy-butyric acid tert-butyl ester

Conditions	Yield
With N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline In N,N-dimethyl-formamide at 20℃;	92%

(2S,3R)-tert-butyl 2-amino-3-tert-butoxybutanoate (5854-78-4) + (2E,4E)-dodeca-2,4-dien-11-ynoic acid → tert-butyl O-(tert-butyl)-N-((2E,4E)-dodeca-2,4-dien-11-ynoyl)-L-threoninate

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 N,N-dimethyl-formamide at 20℃; for 2.5h; Inert atmosphere;	90%

(2S,3R)-tert-butyl 2-amino-3-tert-butoxybutanoate (5854-78-4) + isonicotinoyl chloride hydrochloride (39178-35-3) → C18H28N2O4

Conditions	Yield
With triethylamine In dichloromethane at 20℃; for 2.25h;	88.6%

(2S,3R)-tert-butyl 2-amino-3-tert-butoxybutanoate (5854-78-4) + 2-Nitrobenzenesulfonyl chloride (1694-92-4) → N-(2-nitrobenzenesulfonyl)-O-t-butyl-L-threonine t-butyl ester

Conditions	Yield
With pyridine In dichloromethane at 20℃; Acylation;	88%

N-[(benzyloxy)carbonyl]-L-alanyl-L-alanine methyl ester (2483-51-4) + (2S,3R)-tert-butyl 2-amino-3-tert-butoxybutanoate (5854-78-4) → C26H41N3O7

Conditions	Yield
With 2,2':6',2'':6'',2'''-quaterpyridine; pentamethoxy tantalum at 70℃; for 48h;	84%

Z-Lys(Boc)-OH (2389-60-8) + (2S,3R)-tert-butyl 2-amino-3-tert-butoxybutanoate (5854-78-4) → Nα-Z-Nε-BOC-L-lysyl-O-tert-butyl-L-threonine tert-butyl ester (52616-65-6)

Conditions	Yield
With benzotriazol-1-ol; dicyclohexyl-carbodiimide In tetrahydrofuran at 0℃; for 1h; then 3 h at 20 deg C;	82%

(2E,4E)-11-methyldodeca-2,4-dienoic acid + (2S,3R)-tert-butyl 2-amino-3-tert-butoxybutanoate (5854-78-4) → tert-butyl O-(tert-butyl)-N-((2E,4E)-11-methyldodeca-2,4-dienoyl)-L-threoninate

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 N,N-dimethyl-formamide at 20℃; for 4h; Inert atmosphere;	81%

3-benzylamino-propionic acid methyl ester (23574-01-8) + (2S,3R)-tert-butyl 2-amino-3-tert-butoxybutanoate (5854-78-4) → C22H36N2O4

Conditions	Yield
With pentamethoxy tantalum at 60℃; for 48h;	75%

Isotridecanoic Acid (5681-98-1) + (2S,3R)-tert-butyl 2-amino-3-tert-butoxybutanoate (5854-78-4) → tert-butyl O-(tert-butyl)-N-(11-methyldodecanoyl)-L-threoninate

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 N,N-dimethyl-formamide at 20℃; for 4h; Inert atmosphere;	75%

(S)-N-(tert-butoxycarbonyl)alanine methyl ester (28875-17-4) + (2S,3R)-tert-butyl 2-amino-3-tert-butoxybutanoate (5854-78-4) → Boc-L-Ala-L-Thr(t-Bu)-O-t-Bu

Conditions	Yield
With pentamethoxy tantalum In neat (no solvent) at 60℃; for 72h; Inert atmosphere; Sealed tube;	71%

(3R,4R)-1-(4-fluorophenyl)-3-[(4-fluorobenzoyl)methylthio]-4-{4-[N-(carboxymethyl)carbamoylmethoxy]phenyl}azetidin-2-one (858104-55-9) + (2S,3R)-tert-butyl 2-amino-3-tert-butoxybutanoate (5854-78-4) → N-{[4-((2R,3R)-1-(4-fluorophenyl)-3-{[2-(4-fluorophenyl)-2-oxoethyl]thio}-4-oxoazetidin-2-yl)phenoxy]acetyl}glycyl-L-threonine

Conditions

Yield

Stage #1: (3R,4R)-1-(4-fluorophenyl)-3-[(4-fluorobenzoyl)methylthio]-4-{4-[N-(carboxymethyl)carbamoylmethoxy]phenyl}azetidin-2-one; (2S,3R)-tert-butyl 2-amino-3-tert-butoxybutanoate With 4-methyl-morpholine In dichloromethane at 20℃; Stage #2: With (1,1,1-Benzotriazol-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate In dichloromethane Stage #3: With trifluoroacetic acid In dichloromethane for 2h;

63%

(2S,3R)-tert-butyl 2-amino-3-tert-butoxybutanoate (5854-78-4) + tert-butyl (S)-(1-((2,2-dicyanoethyl)amino)-1-oxo-3-phenylpropan-2-yl)carbamate → tert-butyl N-(tert-butoxycarbonyl)-L-phenylalanylglycyl-O-(tert-butyl)-L-threoninate

Conditions	Yield
With oxygen; cesium acetate In water; N,N-dimethyl-formamide at 20℃; for 17h; Inert atmosphere;	51%

(2S,3R)-tert-butyl 2-amino-3-tert-butoxybutanoate (5854-78-4) + allyl alcohol (107-18-6) → (2S, 3R)-tert-butyl 3-(tert-butoxy)-2-((3-hydroxypropyl)amino)butanoate

Conditions	Yield
With potassium phosphate; [(bis(2-dicyclohexylphosphinoethyl)amine)Fe(CO)Br2]; sodium triethylborohydride In cyclohexane at 80℃; for 24h; Inert atmosphere; Sealed tube;	42%

(2S,3R)-tert-butyl 2-amino-3-tert-butoxybutanoate (5854-78-4) + N-tert-butoxycarbonylglycylglycylphenylalanylmethionine (68800-26-0) → Boc-Gly-Gly-Phe-Met-Thr(tBu)-OtBu

Conditions	Yield
With benzotriazol-1-ol; dicyclohexyl-carbodiimide In N,N-dimethyl-formamide 1.) 30 min, -20 deg C; 2.) 0 deg C, 2 h; 3.) r.t., 18 h;	36.1%

N-benzyloxycarbonyl-L-asparagine p-nitrophenyl ester (3256-57-3) + (2S,3R)-tert-butyl 2-amino-3-tert-butoxybutanoate (5854-78-4) → N-Benzyloxycarbonyl-L-asparaginyl-O-tert.-butyl-L-threonin-tert.-butylester (2596-12-5)

Conditions	Yield
In N,N-dimethyl-formamide

(2S,3R)-tert-butyl 2-amino-3-tert-butoxybutanoate (5854-78-4) → L-threonine (72-19-5)

Conditions	Yield
With trifluoroacetic acid

chloro-trimethyl-silane (75-77-4) + (2S,3R)-tert-butyl 2-amino-3-tert-butoxybutanoate (5854-78-4) → N-(Trimethylsilyl)-O-tert-butylthreonin-tert-butylester

Conditions	Yield
With triethylamine In dichloromethane

(2S,3R)-tert-butyl 2-amino-3-tert-butoxybutanoate (5854-78-4) + Fmoc-Val-OPfp (86060-87-9) → Fmoc-Val-Thr(t-Bu)-O-Bu-t (557095-67-7)

(2S,3R)-tert-butyl 2-amino-3-tert-butoxybutanoate (5854-78-4) + Nα-benzyloxycarbonyl-glycyl-prolyl-alanine (5891-41-8) → Nα-benzyloxycarbonyl-glycyl-prolyl-alanyl-O-tert-butyl-threonine tert-butyl ester (79141-72-3)

Conditions	Yield
With benzotriazol-1-ol; dicyclohexyl-carbodiimide 1.) DMF/CH2Cl2, 0 deg C, 20 min, 2.) room temp., 12 h; Yield given. Multistep reaction;

Upstream product

• 14437-51-5 N-Carbobenzoxy-O-tert.-butyl-L-threonin-tert.-butylester 
• 72-19-5 L-threonine 
• 1634-04-4 tert-butyl methyl ether 
• 17083-30-6 tert-butyl (2S,3R)-2-amino-3-hydroxybutanoate 
• 115-11-7 isobutene 
• 19728-63-3 N-benzyloxycarbonyl-L-treonine 

Downstream Products

• 114691-69-9 o-nitrophenylsulfenyl-O-tert-butyl-L-threonine tert-butyl ester 
• 79141-72-3 N^α-benzyloxycarbonyl-glycyl-prolyl-alanyl-O-tert-butyl-threonine tert-butyl ester 
• 87720-56-7 t-butyl-N-fluoren-9-ylmethyloxycarbonyl-L-phenylalanyl-O-t-butyl-L-threonine 
• 2596-12-5 N-Benzyloxycarbonyl-L-asparaginyl-O-tert.-butyl-L-threonin-tert.-butylester 
• 93-91-4 1-phenylbutan-1,3-dione 
• 1202237-10-2 C₁₉H₂₈N₂O₇ 

Relevant articles and documents

Method for continuously producing O-tert-butyl-L-threonine tert-butyl ester

The invention relates to a method for continuously producing O-tert-butyl-L-threonine tert-butyl ester. By selecting ZSM-5 supported silicotungstic acid as a catalyst and adopting a mode of connectingtwo tubular reactions in series, the invention provides the method for continuously producing O-tert-butyl-L-threonine tert-butyl ester, wherein the method is suitable for industrial production, theyield of the preparation method is greater than 80%, the purity is greater than 99%, and the preparation method is simple in process and suitable for industrial production requirements.

An efficient synthesis of tert-butyl ethers/esters of alcohols/amino acids using methyl tert-butyl ether

A facile synthesis of a wide variety of tert-butyl ethers and tert-butyl ester derivatives under mild conditions is described. Alcohols etherified with tert-butyl methyl ether as tert-butyl source and solvent, in the presence of sulfuric acid. Many amino acid tert-butyl esters have been synthesized by this procedure. The reaction is simple, inexpensive, easily scaled up, and proceeds without observable racemization. A green method was developed for the deprotection of this group using Amberlite resin IR 120-H as catalyst.

Synthesis and biological activities of TAN-1511 analogues

TAN-1511 analogues were synthesized and their effects on the proliferation of bone marrow cells were examined. To exert potent activity the following conditions are necessary: the configuration of the 2-amino-6,7-dihydroxy-4-thiaheptanoic acid moiety must be (2R,6R), long chain acyl groups (C14 to C18) must be bound to both hydroxyl groups, the amino group must be free or acylated with the long chain fatty acid (ca. C14) and the peptide moiety must have glutamic acid as a component. Among the synthesized compounds, trisodium (2R,6R)-2-amino-6,7-bis (hexadecanoyloxy)-4-thiaheptanoyl glycyl glutamyl glutamate, which has improved solubility, was effective in experimental leukocytopenia in mice.