71839-12-8

Basic information

• Product Name: 4-(Butylamino)-benzoic acid, methyl ester
• Synonyms: 4-(Butylamino)-benzoic acid, methyl ester;Benzoic acid, 4-(butylamino)-, methyl ester;Methyl 4-(butylaMino)benzoate;N-Butyl-4-(methoxycarbonyl)aniline
• CAS NO: 71839-12-8
• Molecular Formula: C₁₂H₁₇NO₂
• Molecular Weight: 207
• Mol File: 71839-12-8.mol
• Article Data: 12

Chemical Properties

• Melting Point: 104℃
• Boiling Point: 323.3 °C at 760 mmHg
• Flash Point: 149.3 °C
• Appearance: /
• Density: 1.055
• Vapor Pressure: 0.000264mmHg at 25°C
• Refractive Index: 1.539
• Storage Temp.: -20°C Freezer
• Solubility: Chloroform (Slightly), Methanol (Slightly)
• PKA: 2.61±0.32(Predicted)
• CAS DataBase Reference: 4-(Butylamino)-benzoic acid, methyl ester(CAS DataBase Reference)
• NIST Chemistry Reference: 4-(Butylamino)-benzoic acid, methyl ester(71839-12-8)
• EPA Substance Registry System: 4-(Butylamino)-benzoic acid, methyl ester(71839-12-8)

Safety Data

• Hazardous Substances Data: 71839-12-8(Hazardous Substances Data)

Usage

Uses

Methyl 4-(Butylamino)benzoate is used as a reactant in organic synthesis.

InChI:InChI=1/C12H17NO2/c1-3-4-9-13-11-7-5-10(6-8-11)12(14)15-2/h5-8,13H,3-4,9H2,1-2H3

Synthetic route

tri-n-butylindium (15676-66-1) + 4-methoxycarbonylbenzenediazonium o-benzenedisulfonimide → o-benzenedisulfonimide (4482-01-3) + N-(n-butyl)-4-methoxycarbonylaniline (71839-12-8)

Conditions	Yield
In tetrahydrofuran at 20 - 25℃;	A n/a B 92%

Methyl 4-chlorobenzoate (1126-46-1) + N-butylamine (109-73-9) → N-(n-butyl)-4-methoxycarbonylaniline (71839-12-8)

Conditions	Yield
With di-tert-butyl{2′-isopropoxy-[1,1′-binaphthalen]-2-yl}phosphane; caesium carbonate; palladium diacetate In 1,2-dimethoxyethane at 110℃; for 16h;	91%
With 1,4-diaza-bicyclo[2.2.2]octane; nickel(II) bromide dimethoxyethane; tris(2,2-bipyridine)ruthenium(II) hexafluorophosphate In dimethyl sulfoxide at 80℃; for 1h; Flow reactor; Sealed tube; Schlenk technique; Inert atmosphere; Irradiation;	65%

methyl 4-iodobenzoate (619-44-3) + N-butylamine (109-73-9) → N-(n-butyl)-4-methoxycarbonylaniline (71839-12-8)

Conditions	Yield
Stage #1: methyl 4-iodobenzoate With copper(l) iodide; L-proline In dimethyl sulfoxide at 20℃; for 0.0833333h; Ullmann-Goldberg Substitution; Inert atmosphere; Stage #2: N-butylamine In dimethyl sulfoxide at 20℃; for 17h; Ullmann-Goldberg Substitution; Inert atmosphere;	91%

methyl 4-butyramidobenzoate (356100-70-4) → N-(n-butyl)-4-methoxycarbonylaniline (71839-12-8)

Conditions	Yield
With borane-ammonia complex; boron trifluoride diethyl etherate; tris(pentafluorophenyl)borate In 1,2-dichloro-ethane at 60℃; for 16h;	84%

n-butyllithium (109-72-8, 29786-93-4) + C12H16N2O2S (581798-27-8) → N-(n-butyl)-4-methoxycarbonylaniline (71839-12-8)

Conditions	Yield
In diethyl ether; hexane at -78 - 25℃; for 0.833333h;	67%

N-butylamine (109-73-9) + 4-methoxycarbonyl aniline (619-45-4) → N-(n-butyl)-4-methoxycarbonylaniline (71839-12-8)

Conditions	Yield
With palladium on activated charcoal In tetrahydrofuran at 170℃; for 1.5h; Microwave irradiation;	34%
Stage #1: N-butylamine; 4-methoxycarbonyl aniline In ethanol for 2h; Reflux; Stage #2: With sodium tetrahydroborate In methanol at 0 - 20℃; for 2h;	30%

methanol (67-56-1) + 4-butylamino-benzoyl chloride ; hydrochloride → N-(n-butyl)-4-methoxycarbonylaniline (71839-12-8)

Conditions	Yield
With diethyl ether

butyraldehyde (123-72-8) + 4-methoxycarbonyl aniline (619-45-4) → N-(n-butyl)-4-methoxycarbonylaniline (71839-12-8)

Conditions	Yield
With acetic acid; zinc; benzene

methanol (67-56-1) + 4-(N-butylamino)benzoic acid (4740-24-3) → N-(n-butyl)-4-methoxycarbonylaniline (71839-12-8)

Conditions	Yield
With sulfuric acid Heating;

4-methoxycarbonylbenzenediazonium o-benzenedisulfonimide → N-(n-butyl)-4-methoxycarbonylaniline (71839-12-8)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: NaOMe / methanol 1.2: 80 percent / methanol / 0.5 h / 20 - 25 °C 2.1: 67 percent / diethyl ether; hexane / 0.83 h / -78 - 25 °C View Scheme

4-methoxycarbonyl aniline (619-45-4) → N-(n-butyl)-4-methoxycarbonylaniline (71839-12-8)

Conditions	Yield
Multi-step reaction with 3 steps 1: triethylamine / dichloromethane / 14 h / 0 - 20 °C 2: caesium carbonate / N,N-dimethyl-formamide / 2 h / 90 °C 3: potassium carbonate / methanol / 1 h / 70 °C View Scheme

methyl 4-(2,2,2-trifluoroacetamido)benzoate (304646-56-8) → N-(n-butyl)-4-methoxycarbonylaniline (71839-12-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: caesium carbonate / N,N-dimethyl-formamide / 2 h / 90 °C 2: potassium carbonate / methanol / 1 h / 70 °C View Scheme

C14H16F3NO3 → N-(n-butyl)-4-methoxycarbonylaniline (71839-12-8)

Conditions	Yield
With potassium carbonate In methanol at 70℃; for 1h;	702.6 mg

methyl 4-butyramidobenzoate (356100-70-4) → N-(n-butyl)-4-methoxycarbonylaniline (71839-12-8) + 4-methoxycarbonyl aniline (619-45-4)

Conditions	Yield
With [bis(2-methylallyl)cycloocta-1,5-diene]ruthenium(II); formic acid; bis(trifluoromethanesulfonyl)amide; triethylamine; [2-((diphenylphospino)methyl)-2-methyl-1,3-propanediyl]bis[diphenylphosphine] In dibutyl ether at 130℃; for 24h; Overall yield = 83 percent; Overall yield = 43 mg;

2-bromo-1-cycloheptene-1-carboxylic acid (90002-61-2) + N-(n-butyl)-4-methoxycarbonylaniline (71839-12-8) → methyl 4-(2-bromo-N-butylcyclohept-1-ene-1-carboxamido)benzoate (1616681-30-1)

Conditions	Yield
Stage #1: 2-bromo-1-cycloheptene-1-carboxylic acid With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 20℃; for 0.166667h; Stage #2: N-(n-butyl)-4-methoxycarbonylaniline With dmap In dichloromethane at 60℃; for 2h;	97%

2-bromo-1-cyclopentene-1-carboxylic acid (1506-75-8) + N-(n-butyl)-4-methoxycarbonylaniline (71839-12-8) → methyl 4-(2-bromo-N-butylcyclopent-1-ene-1-carboxamido)benzoate (1616681-26-5)

Conditions	Yield
Stage #1: 2-bromo-1-cyclopentene-1-carboxylic acid With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 20℃; for 0.166667h; Stage #2: N-(n-butyl)-4-methoxycarbonylaniline With dmap In dichloromethane at 60℃; for 2h;	92%

N-(n-butyl)-4-methoxycarbonylaniline (71839-12-8) + benzylamine (100-46-9) → C18H22N2O (1470025-87-6)

Conditions	Yield
With [m-(1,4-diazabicyclo[2.2.2]octanekN1:kN4)]hexamethyldialuminum In tetrahydrofuran at 130℃; for 0.133333h; Inert atmosphere; Microwave irradiation;	91%

N-(n-butyl)-4-methoxycarbonylaniline (71839-12-8) + Propargylamine (2450-71-7) → C14H18N2O (1470025-88-7)

Conditions	Yield
With [m-(1,4-diazabicyclo[2.2.2]octanekN1:kN4)]hexamethyldialuminum In tetrahydrofuran at 130℃; for 0.133333h; Inert atmosphere; Microwave irradiation;	89%

2-bromocyclohex-1-enecarboxylic acid (68965-62-8) + N-(n-butyl)-4-methoxycarbonylaniline (71839-12-8) → methyl 4-(2-bromo-N-butylcyclohex-1-ene-1-carboxamido)benzoate (1616681-28-7)

Conditions	Yield
Stage #1: 2-bromocyclohex-1-enecarboxylic acid With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 20℃; for 0.166667h; Stage #2: N-(n-butyl)-4-methoxycarbonylaniline With dmap In dichloromethane at 60℃; for 2h;	84%

2-(N,N-dimethylamino)ethanol (108-01-0) + N-(n-butyl)-4-methoxycarbonylaniline (71839-12-8) → tetracaine hydrochloride (136-47-0)

Conditions	Yield
Stage #1: 2-(N,N-dimethylamino)ethanol; N-(n-butyl)-4-methoxycarbonylaniline With sodium methylate at 130℃; for 8h; Stage #2: With hydrogenchloride	83%

isocyanic acid (3-nitro-phenyl) ester (3320-87-4) + N-(n-butyl)-4-methoxycarbonylaniline (71839-12-8) → methyl 4-[1-butyl-3-(3-nitrophenyl)ureido]benzoate

Conditions	Yield
In dichloromethane at 20℃; Inert atmosphere;	80%

2-bromo-1-cyclooctene-1-carboxylic acid (1259296-21-3) + N-(n-butyl)-4-methoxycarbonylaniline (71839-12-8) → methyl 4-(2-bromo-N-butylcyclooct-1-ene-1-carboxamido)benzoate (1616681-32-3)

Conditions	Yield
Stage #1: 2-bromo-1-cyclooctene-1-carboxylic acid With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 20℃; for 0.166667h; Stage #2: N-(n-butyl)-4-methoxycarbonylaniline With dmap In dichloromethane at 60℃; for 2h;	56%

Malonic acid monomethyl ester (16695-14-0) + N-(n-butyl)-4-methoxycarbonylaniline (71839-12-8) → N-butyl-N-(4-methoxycarbonylphenyl)-α-carbomethoxyacetamide (155257-37-7)

Conditions	Yield
With dmap; dicyclohexyl-carbodiimide In dichloromethane 15 min, 0 deg C then r.t., 5 h;

N-(n-butyl)-4-methoxycarbonylaniline (71839-12-8) → C11H17N3O

Conditions	Yield
With hydrazine hydrate for 0.5h; Heating;

N-(n-butyl)-4-methoxycarbonylaniline (71839-12-8) → 1-butyl-5-(methoxycarbonyl)-2(3H)-indolinone

Conditions	Yield
Multi-step reaction with 3 steps 1: DMAP, DCC / CH2Cl2 / 15 min, 0 deg C then r.t., 5 h 2: MeSO2N3, DBU / acetonitrile / 0 deg C, 30 min then r.t. 3: 50 percent / 50 molpercent Nafion-H / toluene / 28 h / Heating View Scheme

N-(n-butyl)-4-methoxycarbonylaniline (71839-12-8) → N-butyl-N-(4-methoxycarbonylphenyl)-α-carbomethoxy-α-diazoacetamide (148518-83-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: DMAP, DCC / CH2Cl2 / 15 min, 0 deg C then r.t., 5 h 2: MeSO2N3, DBU / acetonitrile / 0 deg C, 30 min then r.t. View Scheme

N-(n-butyl)-4-methoxycarbonylaniline (71839-12-8) → 1-(4-carbomethoxyphenyl)-3-carbomethoxy-4-propyl-2-azetidinone

Conditions	Yield
Multi-step reaction with 3 steps 1: DMAP, DCC / CH2Cl2 / 15 min, 0 deg C then r.t., 5 h 2: MeSO2N3, DBU / acetonitrile / 0 deg C, 30 min then r.t. 3: 10 percent / 50 molpercent Nafion-H / toluene / 28 h / Heating View Scheme

N-(n-butyl)-4-methoxycarbonylaniline (71839-12-8) → methyl 5-butyl-4-oxo-2,3,4,5-tetrahydro-1H-cyclopenta[c]quinoline-8-carboxylate (1616681-34-5)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: oxalyl dichloride; N,N-dimethyl-formamide / dichloromethane / 0.17 h / 20 °C 1.2: 2 h / 60 °C 2.1: palladium diacetate; caesium carbonate; tricyclohexylphosphine tetrafluoroborate / N,N-dimethyl acetamide / 4 h / 130 °C View Scheme

N-(n-butyl)-4-methoxycarbonylaniline (71839-12-8) → methyl 5-butyl-6-oxo-5,6,7,8,9,10-hexahydrophenanthridine-2-carboxylate (1616681-36-7)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: oxalyl dichloride; N,N-dimethyl-formamide / dichloromethane / 0.17 h / 20 °C 1.2: 2 h / 60 °C 2.1: palladium diacetate; caesium carbonate; tricyclohexylphosphine tetrafluoroborate / N,N-dimethyl acetamide / 4 h / 130 °C View Scheme

N-(n-butyl)-4-methoxycarbonylaniline (71839-12-8) → methyl 5-butyl-6-oxo-6,7,8,9,10,11-hexahydro-5H-cyclohepta[c]quinoline-2-carboxylate (1616681-38-9)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: oxalyl dichloride; N,N-dimethyl-formamide / dichloromethane / 0.17 h / 20 °C 1.2: 2 h / 60 °C 2.1: palladium diacetate; caesium carbonate; tricyclohexylphosphine tetrafluoroborate / N,N-dimethyl acetamide / 4 h / 130 °C View Scheme

N-(n-butyl)-4-methoxycarbonylaniline (71839-12-8) → methyl 5-butyl-6-oxo-5,6,7,8,9,10,11,12-octahydrocycloocta[c]quinoline-2-carboxylate (1616681-40-3)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: oxalyl dichloride; N,N-dimethyl-formamide / dichloromethane / 0.17 h / 20 °C 1.2: 2 h / 60 °C 2.1: palladium diacetate; caesium carbonate; tricyclohexylphosphine tetrafluoroborate / N,N-dimethyl acetamide / 4 h / 130 °C View Scheme

Upstream product

• 67-56-1 methanol 
• 1126-46-1 Methyl 4-chlorobenzoate 
• 109-73-9 N-butylamine 
• 356100-70-4 methyl 4-butyramidobenzoate 
• 619-44-3 methyl 4-iodobenzoate 
• 304646-56-8 methyl 4-(2,2,2-trifluoroacetamido)benzoate 
• 619-45-4 4-methoxycarbonyl aniline 
• 15676-66-1 tri-n-butylindium 
• 4740-24-3 4-(N-butylamino)benzoic acid 
• 109-72-8 n-butyllithium 
• 581798-27-8 C₁₂H₁₆N₂O₂S 
• 123-72-8 butyraldehyde 

Downstream Products

• 1616681-26-5 methyl 4-(2-bromo-N-butylcyclopent-1-ene-1-carboxamido)benzoate 
• 1616681-28-7 methyl 4-(2-bromo-N-butylcyclohex-1-ene-1-carboxamido)benzoate 
• 1616681-30-1 methyl 4-(2-bromo-N-butylcyclohept-1-ene-1-carboxamido)benzoate 
• 1616681-32-3 methyl 4-(2-bromo-N-butylcyclooct-1-ene-1-carboxamido)benzoate 
• 1616680-38-6 N-phenyl-5-butyl-6-oxo-6,7,8,9,10,11-hexahydro-5H-cyclohepta[c]quinoline-2-carboxamide 
• 1616680-46-6 N-c-hexyl-5-butyl-6-oxo-6,7,8,9,10,11-hexahydro-5H-cyclohepta[c]quinoline-2-carboxamide 
• 136-47-0 tetracaine hydrochloride 
• 1470025-87-6 C₁₈H₂₂N₂O 
• 1470025-88-7 C₁₄H₁₈N₂O 
• 148518-83-6 N-butyl-N-(4-methoxycarbonylphenyl)-α-carbomethoxy-α-diazoacetamide 
• 155257-37-7 N-butyl-N-(4-methoxycarbonylphenyl)-α-carbomethoxyacetamide 

Relevant articles and documents

Visible Light-Mediated (Hetero)aryl Amination Using Ni(II) Salts and Photoredox Catalysis in Flow: A Synthesis of Tetracaine

We report a visible light-mediated flow process for C-N cross-coupling of (hetero)aryl halides with a variety of amine coupling partners through the use of a photoredox/nickel dual catalyst system. Compared to the method in batch, this flow process enables a broader substrate scope, including less-activated (hetero)aryl bromides and electron-deficient (hetero)aryl chlorides, and significantly reduced reaction times (10 to 100 min). Furthermore, scale up of the reaction, demonstrated through the synthesis of tetracaine, is easily achieved, delivering the C-N cross-coupled products in consistently high yield of 84% on up to a 10 mmol scale.

B(C6F5)3-Catalyzed Deoxygenative Reduction of Amides to Amines with Ammonia Borane

The first B(C6F5)3-catalyzed deoxygenative reduction of amides into the corresponding amines with readily accessible and stable ammonia borane (AB) as a reducing agent under mild reaction conditions is reported. This metal-free protocol provides facile access to a wide range of structurally diverse amine products in good to excellent yields, and various functional groups including those that are reduction-sensitive were well tolerated. This new method is also applicable to chiral amide substrates without erosion of the enantiomeric purity. The role of BF3 ? OEt2 co-catalyst in this reaction is to activate the amide carbonyl group via the in situ formation of an amide-boron adduct. (Figure presented.).

Room-Temperature Practical Copper-Catalyzed Amination of Aryl Iodides

An efficient and highly practical procedure is reported for the Ullmann-Goldberg-type copper-catalyzed amination of aryl iodides. By using a combination of copper iodide and proline in the presence of an excess of an amine, a wide range of aryl iodides can be readily aminated at room temperature. The reaction proceeds well regardless of the electronic properties of the starting aryl iodide and the amination products can be obtained without the need for purification by column chromatography in most cases. Owing to its efficiency and the mildness of the reaction conditions, this amination could also be extended to the amination of complex aryl iodides at room temperature.