7462-86-4

Basic information

• Product Name: Methyl 4-piperidinecarboxylate
• Synonyms: METHYL ISONIPECOTATE HYDROCHLORIDE;METHYL ISONIPECOTINATE HYDROCHLORIDE;METHYL 4-PIPERIDINECARBOXYLATE HCL;Methyl Isonipecotate HCl;Methyl 4-Piperidinecarboxylic Ester HCl;Methyl 4-piperidinecarboxylate hydrochloride;methyl piperidine-4-carboxylate hydrochloride;4-PIPERIDINECARBOXYLIC ACID METHYL ESTER HYDROCHLORIDE
• CAS NO: 7462-86-4
• Molecular Formula: C₇H₁₃NO₂*ClH
• Molecular Weight: 179.64
• EINECS: 203-126-8
• Product Categories: Esters;Pyrans, Piperidines &Piperazines;Pyrans, Piperidines & Piperazines
• Mol File: 7462-86-4.mol
• Article Data: 10

Chemical Properties

• Melting Point: 160°C
• Boiling Point: 85-90 °C
• Flash Point: 89 °C
• Appearance: /
• Density: 1.06
• Vapor Pressure: 0.0408mmHg at 25°C
• Refractive Index: 1.465
• Storage Temp.: under inert gas (nitrogen or Argon) at 2-8°C
• CAS DataBase Reference: Methyl 4-piperidinecarboxylate(CAS DataBase Reference)
• NIST Chemistry Reference: Methyl 4-piperidinecarboxylate(7462-86-4)
• EPA Substance Registry System: Methyl 4-piperidinecarboxylate(7462-86-4)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-36
• Hazardous Substances Data: 7462-86-4(Hazardous Substances Data)

Usage

General Description

Methyl 4-piperidinecarboxylate is an organic chemical compound that consists of a piperidine ring with a carboxylate ester functional group. It is commonly used as an intermediate in the synthesis of pharmaceutical drugs and other organic compounds. Methyl 4-piperidinecarboxylate has a variety of applications, including as a building block in the production of substances such as muscle relaxants and antihistamines. It is also used in the development of insecticides and as a flavor and fragrance ingredient. Due to its versatility and utility as a precursor in organic synthesis, methyl 4-piperidinecarboxylate is a valuable and important chemical compound in the pharmaceutical and chemical industries.

InChI:InChI=1/C7H13NO2.ClH/c1-10-7(9)6-2-4-8-5-3-6;/h6,8H,2-5H2,1H3;1H

Synthetic route

1-tert-Butyl 4-methyl piperidine-1,4-dicarboxylate (124443-68-1) → methyl piperidine-4-carboxylate hydrochloride (7462-86-4)

Conditions	Yield
With hydrogenchloride In dichloromethane; ethyl acetate at 20℃; for 1.5h; Inert atmosphere;	99%
With hydrogenchloride In dichloromethane; ethyl acetate at 20℃; for 1.5h;	99%
With hydrogenchloride In 1,4-dioxane at 20℃; for 4h;	99.57%

methanol (67-56-1) + isonipecotic acid (498-94-2) → methyl piperidine-4-carboxylate hydrochloride (7462-86-4)

Conditions	Yield
With thionyl chloride at 80℃; for 3h;	98.8%
With thionyl chloride for 2h; Reflux;	98.4%
With thionyl chloride at 20℃; for 20h; Esterification;	84%

isonipecotic acid (498-94-2) → methyl piperidine-4-carboxylate hydrochloride (7462-86-4)

Conditions	Yield
In tetrahydrofuran; hydrogenchloride; methanol; water

methyl piperidine-4-carboxylate hydrochloride (7462-86-4) + benzyl bromide (100-39-0) → 1-benzyl-4-piperidinecarboxylic acid methyl ester (10315-06-7)

Conditions	Yield
With triethylamine In methanol for 6h; Reflux;	94.2%
With triethylamine In dichloromethane at 20℃; Alkylation;	79.7%
With triethylamine In dichloromethane at 10 - 20℃;

methyl piperidine-4-carboxylate hydrochloride (7462-86-4) + 2,2-dimethylpropanoic anhydride (1538-75-6) → 1-tert-Butyl 4-methyl piperidine-1,4-dicarboxylate (124443-68-1)

Conditions	Yield
With sodium hydroxide In tert-butyl alcohol for 48h;	92%

methyl piperidine-4-carboxylate hydrochloride (7462-86-4) + benzyl chloroformate (501-53-1) → piperidine-1,4-dicarboxylic acid 1-benzyl ester 4-methyl ester (138163-07-2)

Conditions	Yield
Stage #1: methyl piperidine-4-carboxylate hydrochloride With sodium hydrogencarbonate In 1,4-dioxane; water at 0 - 5℃; Stage #2: benzyl chloroformate In 1,4-dioxane; water at 0 - 20℃; for 24h;	85%

methyl piperidine-4-carboxylate hydrochloride (7462-86-4) + (3R,5S)-7-chloro-5-(2,3-dimethoxyphenyl)-1-(3-hydroxy-2,2-dimethylpropyl)-2-oxo-1,2,3,5-tetrahydro-4,1-benzoxazepine-3-acetic acid (189060-51-3) → methyl 1-[[(3R,5S)-7-chloro-5-(2,3-dimethoxyphenyl)-1-(3-hydroxy-2,2-dimethylpropyl)-2-oxo-1,2,3,5-tetrahydro-4,1-benzoxazepin-3-yl]acetyl]piperidine-4-carboxylate (189059-66-3)

Conditions	Yield
With diethylphosphoryl cyanide; triethylamine In N,N-dimethyl-formamide at 20℃; for 0.5h;	79%

(S)-5-(1-((tert-butoxycarbonyl)amino)ethyl)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-1,3-oxazole-4-carboxylic acid + methyl piperidine-4-carboxylate hydrochloride (7462-86-4) → (S)-methyl 1-(5-(1-((tert-butoxycarbonyl)amino)ethyl)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-1,3-oxazole-4-carbonyl)piperidine-4-carboxylate

Conditions	Yield
With 1-hydroxy-7-aza-benzotriazole; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In dichloromethane at 0 - 20℃; for 12h; Inert atmosphere;	78%
With 1-hydroxy-7-aza-benzotriazole; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In dichloromethane at 0 - 20℃; for 12h;	78%

methyl piperidine-4-carboxylate hydrochloride (7462-86-4) + pivaloyl chloride (3282-30-2) → methyl 1-pivaloylpiperidine-4-carboxylate (505088-49-3)

Conditions	Yield
Stage #1: methyl piperidine-4-carboxylate hydrochloride With N-ethyl-N,N-diisopropylamine In dichloromethane for 0.166667h; Stage #2: pivaloyl chloride In dichloromethane at 20℃;	77%

methyl piperidine-4-carboxylate hydrochloride (7462-86-4) + 4-bromo-3-fluoroiodobenzene (136434-77-0) → methyl 1-(4-bromo-3-fluorophenyl)piperidine-4-carboxylate

Conditions	Yield
With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene In 1,4-dioxane at 110℃; for 12h; Inert atmosphere;	74%
With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene In 1,4-dioxane at 110℃; for 12h;	74%

2-((2S,4R)-1-(5-((S)-1-((tert-butoxycarbonyl)amino)ethyl)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)oxazole-4-carbonyl)-4-((methoxycarbonyl)amino)pyrrolidin-2-yl)acetic acid + methyl piperidine-4-carboxylate hydrochloride (7462-86-4) → methyl 1-(2-((2S,4R)-1-(5-((S)-1-((tert-butoxycarbonyl)amino)ethyl)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)oxazole-4-carbonyl)-4-((methoxycarbonyl)amino)pyrrolidin-2-yl)acetyl)piperidine-4-carboxylate

Conditions	Yield
With 1-hydroxy-7-aza-benzotriazole; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 10h; Cooling with ice;	73%

6-fluoropyridine-3-sulfonyl chloride (1025509-80-1) + methyl piperidine-4-carboxylate hydrochloride (7462-86-4) → 1-(6-fluoro-pyridine-3-sulfonyl)-piperidine-4-carboxylic acid methyl ester

Conditions	Yield
With triethylamine In dichloromethane at 22℃; for 0.75h; Inert atmosphere;	73%
With triethylamine In dichloromethane at 22℃; for 0.75h;	73%

3-bromopropanol methyl ether (36865-41-5) + methyl piperidine-4-carboxylate hydrochloride (7462-86-4) → methyl-1-(3-methoxypropyl)piperidine-4-carboxylate

Conditions	Yield
With potassium carbonate In methanol at 75℃;	72.2%

1-(2,5-bis(trifluoromethyl)phenyl)ethyl methanesulfonate + methyl piperidine-4-carboxylate hydrochloride (7462-86-4) → methyl 1-(1-(2,5-bis(trifluoromethyl)phenyl)ethyl)piperidine-4-carboxylate

Conditions	Yield
With potassium carbonate; sodium iodide In acetonitrile at 85℃; for 12h;	71%

(R)-tert-butyl 2-(3-bromo-5-fluorophenyl)-3-oxohexahydroimidazo[1,5-a]pyrazine-7(1H)-carboxylate + methyl piperidine-4-carboxylate hydrochloride (7462-86-4) → (R)-tert-butyl 2-(3-fluoro-5-(4-(methoxycarbonyl)piperidin-1-yl)phenyl)-3-oxohexahydroimidazo[1,5-a]pyrazine-7(1H)-carboxylate

Conditions	Yield
With palladium diacetate; caesium carbonate; tert-butyl XPhos In 1,4-dioxane at 90℃; for 12h; Inert atmosphere;	70%

methyl piperidine-4-carboxylate hydrochloride (7462-86-4) + C21H19NO9 → 2-ethyl 3,4-dimethyl 5-[2-({1-[4-(methoxycarbonyl)piperidin-1-yl]-1-oxopropan-2-yl}carbamoyl)phenyl]furan-2,3,4-tricarboxylate

Conditions	Yield
With triethylamine In dichloromethane at 20℃; for 0.0833333h;	66%

4-methoxyphenethyl bromide (14425-64-0) + methyl piperidine-4-carboxylate hydrochloride (7462-86-4) → 1-[2-(4-methoxyphenyl)-ethyl]-4-piperidinecarboxylic acid,methyl ester (124461-08-1)

Conditions	Yield
In N,N-dimethyl-formamide at 90℃; for 17h; Heating;	63%
With potassium carbonate In ethyl acetate; N,N-dimethyl-formamide; toluene

2-bromo-6-methyl-pyrazine (914452-71-4) + methyl piperidine-4-carboxylate hydrochloride (7462-86-4) → methyl 1-(6-methylpyrazin-2-yl)piperidine-4-carboxylate

Conditions	Yield
With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene In toluene at 90℃; for 16h;	62.99%

2-(2-amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-6-yl)acetic acid (351185-23-4) + methyl piperidine-4-carboxylate hydrochloride (7462-86-4) → 1-[2-(2-amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-6-yl)acetylamino]piperidine-4-carboxylic acid

Conditions	Yield
Stage #1: 2-(2-amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-6-yl)acetic acid With benzotriazol-1-ol In N,N-dimethyl-formamide at 20℃; for 2h; Stage #2: methyl piperidine-4-carboxylate hydrochloride With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In N,N-dimethyl-formamide at 20℃; for 5h; Stage #3: With sodium hydroxide at 20℃; for 1.5h;	55%

methyl piperidine-4-carboxylate hydrochloride (7462-86-4) + 1,1'-carbonyldiimidazole (530-62-1) → methyl 1-(1H-imidazole-1-carbonyl)piperidine-4-carboxylate

Conditions	Yield
With triethylamine In dichloromethane at 0 - 20℃; Inert atmosphere;	54%

indole (120-72-9) + formaldehyd (50-00-0) + methyl piperidine-4-carboxylate hydrochloride (7462-86-4) → 1-indol-3-ylmethyl-piperidine-4-carboxylic acid methyl ester

methyl piperidine-4-carboxylate hydrochloride (7462-86-4) → piperidine-4-carboxylic acid hydrazide (42596-58-7)

Conditions	Yield
With hydrazine hydrate

methyl piperidine-4-carboxylate hydrochloride (7462-86-4) + 1-[8-(triphenylmethylsulfanyl)octyl]piperazine (337468-25-4) + cyclopentadienyl(1,4-dichlorobenzene)ruthenium hexafluorophosphate → bis[8-[4-[4-(4-methoxycarbonylpiperidino)phenyl]piperazino]octyl]disulfide

Conditions	Yield
Stage #1: 1-[8-(triphenylmethylsulfanyl)octyl]piperazine; cyclopentadienyl(1,4-dichlorobenzene)ruthenium hexafluorophosphate With potassium carbonate In tetrahydrofuran at 20℃; Stage #2: methyl piperidine-4-carboxylate hydrochloride With sodium hydroxide; potassium carbonate In tetrahydrofuran at 65 - 70℃; for 60h; Stage #3: With ammonium hydroxide In acetonitrile for 48h; UV-irradiation;	20 mg

methyl piperidine-4-carboxylate hydrochloride (7462-86-4) → 1-benzyl-4-formylpiperidine (22065-85-6)

Conditions	Yield
Multi-step reaction with 3 steps 1: 79.7 percent / Et3N / CH2Cl2 / 20 °C 2: 69.5 percent / LiAlH4 / tetrahydrofuran / 0.5 h / 50 °C 3: 94.3 percent / oxalyl chloride; dimethyl sulfoxide; Et3N / CH2Cl2 / 0.25 h / -55 °C View Scheme
Multi-step reaction with 5 steps 1.1: triethylamine / methanol / 6 h / Reflux 2.1: water; methanol; sodium hydroxide / 2 h / Reflux 3.1: thionyl chloride / 2 h / Reflux 3.2: 0.5 h / Cooling with ice 4.1: thionyl chloride / 5 h / Reflux 5.1: diisobutylaluminium hydride / toluene / 1 h / 0 °C 5.2: 0.5 h / pH 8 View Scheme

methyl piperidine-4-carboxylate hydrochloride (7462-86-4) → 1-benzyl-4-piperidinemethanol (67686-01-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: 79.7 percent / Et3N / CH2Cl2 / 20 °C 2: 69.5 percent / LiAlH4 / tetrahydrofuran / 0.5 h / 50 °C View Scheme
Multi-step reaction with 2 steps 1: triethylamine / methanol / 6 h / Reflux 2: diisobutylaluminium hydride / toluene / 1 h / 0 °C View Scheme

methyl piperidine-4-carboxylate hydrochloride (7462-86-4) → N-benzyl-4-[hydroxy(3-methoxyphenyl)methyl]piperidine (255723-94-5)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: 79.7 percent / Et3N / CH2Cl2 / 20 °C 2.1: 69.5 percent / LiAlH4 / tetrahydrofuran / 0.5 h / 50 °C 3.1: 94.3 percent / oxalyl chloride; dimethyl sulfoxide; Et3N / CH2Cl2 / 0.25 h / -55 °C 4.1: Mg / tetrahydrofuran / 0.5 h / Heating 4.2: 94.3 percent / tetrahydrofuran / 2 h / 20 °C View Scheme

methyl piperidine-4-carboxylate hydrochloride (7462-86-4) → 3-[(1-benzyl-piperidin-4-yl)-(4-tert-butyl-phenyl)-methyl]-phenol

Conditions

Yield

Multi-step reaction with 6 steps 1.1: 79.7 percent / Et3N / CH2Cl2 / 20 °C 2.1: 69.5 percent / LiAlH4 / tetrahydrofuran / 0.5 h / 50 °C 3.1: 94.3 percent / oxalyl chloride; dimethyl sulfoxide; Et3N / CH2Cl2 / 0.25 h / -55 °C 4.1: Mg / tetrahydrofuran / 0.5 h / Heating 4.2: 94.3 percent / tetrahydrofuran / 2 h / 20 °C 5.1: 94.3 percent / AlCl3 / 0.05 h / Heating 6.1: 31 percent / BBr3 / CH2Cl2 / 1 h / 20 °C View Scheme

methyl piperidine-4-carboxylate hydrochloride (7462-86-4) → N-benzyl-4-(4-tert-butyl-3'-methoxybenzhydryl)piperidine (255723-95-6)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: 79.7 percent / Et3N / CH2Cl2 / 20 °C 2.1: 69.5 percent / LiAlH4 / tetrahydrofuran / 0.5 h / 50 °C 3.1: 94.3 percent / oxalyl chloride; dimethyl sulfoxide; Et3N / CH2Cl2 / 0.25 h / -55 °C 4.1: Mg / tetrahydrofuran / 0.5 h / Heating 4.2: 94.3 percent / tetrahydrofuran / 2 h / 20 °C 5.1: 94.3 percent / AlCl3 / 0.05 h / Heating View Scheme

methyl piperidine-4-carboxylate hydrochloride (7462-86-4) → 4-[[1-[(4-fluorophenyl)methyl]-1H-benzimidazol-2-yl]carbonyl]-1-piperidinecarboxylic acid,1,1-dimethylethyl ester (124443-69-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: 92 percent / 1M aq. NaOH / 2-methyl-propan-2-ol / 48 h 2: 1.) n-BuLi / 1.) -78 deg C, THF, hexane, 15 min 2.) THF, 15 min, -78 deg C View Scheme

methyl piperidine-4-carboxylate hydrochloride (7462-86-4) → [1-[(4-fluorophenyl)methyl]-1H-benzimidazol-2-yl][1-[2-(4-methoxyphenyl)ethyl]-4-piperidinyl]methanone (124461-07-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: 63 percent / dimethylformamide / 17 h / 90 °C / Heating 2: 1.) n-BuLi / 1.) THF, hexane, -78 deg C, 15 min 2.) THF, a) 5-10 min, -78 deg C b) without cooling View Scheme
Multi-step reaction with 4 steps 1: 92 percent / 1M aq. NaOH / 2-methyl-propan-2-ol / 48 h 2: 1.) n-BuLi / 1.) -78 deg C, THF, hexane, 15 min 2.) THF, 15 min, -78 deg C 3: 84 percent / 0.5 h / Ambient temperature 4: 57 percent / K2CO3 / dimethylformamide / 22 h / 90 °C View Scheme

methyl piperidine-4-carboxylate hydrochloride (7462-86-4) → <1-<(4-fluorophenyl)methyl>-1H-benzimidazol-2-yl>-4-piperidinylmethanone mono(trifluoroacetate) (124443-71-6)

Conditions	Yield
Multi-step reaction with 3 steps 1: 92 percent / 1M aq. NaOH / 2-methyl-propan-2-ol / 48 h 2: 1.) n-BuLi / 1.) -78 deg C, THF, hexane, 15 min 2.) THF, 15 min, -78 deg C 3: 84 percent / 0.5 h / Ambient temperature View Scheme

Upstream product

• 67-56-1 methanol 
• 498-94-2 isonipecotic acid 
• 124443-68-1 1-tert-Butyl 4-methyl piperidine-1,4-dicarboxylate 

Downstream Products

• 42596-58-7 piperidine-4-carboxylic acid hydrazide 
• 124461-08-1 1-[2-(4-methoxyphenyl)-ethyl]-4-piperidinecarboxylic acid,methyl ester 
• 124443-68-1 1-tert-Butyl 4-methyl piperidine-1,4-dicarboxylate 
• 1246533-11-8 methyl 1-(3-methoxy-4-nitrophenyl)piperidine-4-carboxylate 
• 88915-26-8 4-aminomethyl-1-benzylpiperidine 

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