498-94-2

Basic information

• Product Name: Isonipecotic acid
• Synonyms: Isonipecotic aci;Isonipecotic acid, 4-Carboxypiperidine;4 - piperidine forMic acid;Inp-OH;Isonipecotic acid≥ 99% (Titration);4-Piperidinecarboxylic acid for synthesis;IsonipecoticAcid98%;4-PiperidinecarboxylicAcid/IsonipecoticAcid
• CAS NO: 498-94-2
• Molecular Formula: C₆H₁₁NO₂
• Molecular Weight: 129.16
• EINECS: 207-872-3
• Product Categories: Nitrogen cyclic compounds;blocks;Carboxes;Heterocycles;Acids and Derivatives;Amines and Anilines;Carboxylic Acids;Pyrans, Piperidines &Piperazines;Piperidine;Organic acids;Terfenadine Fexofenadine Ketanserin;Carboxylic Acids;Pyrans, Piperidines & Piperazines
• Mol File: 498-94-2.mol
• Article Data: 30

Chemical Properties

• Melting Point: >300 °C(lit.)
• Boiling Point: 239.22°C (rough estimate)
• Flash Point: 114.5 °C
• Appearance: White to faint pink-beige/Powder
• Density: 1.1426 (rough estimate)
• Vapor Pressure: 0.0026mmHg at 25°C
• Refractive Index: 1.4587 (estimate)
• Storage Temp.: Store at 0-5°C
• Solubility: Water
• PKA: pK1:3.73(+1);pK2:10.72(0) (25°C)
• Water Solubility: soluble
• Merck: 14,5189
• BRN: 112553
• CAS DataBase Reference: Isonipecotic acid(CAS DataBase Reference)
• NIST Chemistry Reference: Isonipecotic acid(498-94-2)
• EPA Substance Registry System: Isonipecotic acid(498-94-2)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-36-37/39
• WGK Germany: 3
• RTECS: NS5150000
• TSCA: T
• HazardClass: IRRITANT
• Hazardous Substances Data: 498-94-2(Hazardous Substances Data)

Usage

Chemical Properties

white to faint pink-beige powder

Uses

A GABA-A receptor partial agonist

Synthesis Reference(s)

Synthesis, p. 623, 1984Tetrahedron Letters, 35, p. 8783, 1994 DOI: 10.1016/S0040-4039(00)78497-8

Purification Methods

It crystallises from H2O or EtOH as needles. The hydrochloride recrystallises from H2O or aqueous HCl with m 293odec (also 298odec, 300odec). [Wibaut Recl Trav Chim Pays-Bas 63 141 1944, IR: Zacharius et al. J Am Chem Soc 76 2908 1954, Beilstein 22/1 V 244.]

InChI:InChI=1/C6H11NO2/c8-6(9)5-1-3-7-4-2-5/h5,7H,1-4H2,(H,8,9)

Synthetic route

Piperidine-4-carboxylic acid 3-methyl-but-2-enyl ester → isonipecotic acid (498-94-2)

Conditions	Yield
With diethylamine; Pd(0) (in situ from Pd(OAc)2 and m.sulfonated triphenylphosphine) In water; acetonitrile for 0.166667h; 5 molpercent catalyst;	100%

Isonicotinic acid N-oxide (13602-12-5) → isonipecotic acid (498-94-2)

Conditions	Yield
With ammonium formate; 10percent palladium on carbon In methanol at 20℃; for 16h;	99%

benzyl 4-(chlorocarbonyl)piperidine-1-carboxylate (10314-99-5) → isonipecotic acid (498-94-2) + N-(benzyloxycarbonyl)piperidine-4-carboxaldehyde (138163-08-3) + 4-(4-Formyl-piperidine-1-carbonyl)-piperidine-1-carboxylic acid benzyl ester

Conditions	Yield
With methyl-phenyl-thioether; hydrogen; N-ethyl-N,N-diisopropylamine; palladium on activated charcoal In toluene at 20℃; under 2068.6 Torr; for 22h; Yields of byproduct given;	A n/a B 94% C n/a

3-Quinuclidinone (3731-38-2) → isonipecotic acid (498-94-2)

Conditions	Yield
With dihydrogen peroxide In ethanol for 2h;	72%

piperidine (110-89-4) + formic acid (64-18-6) → isonipecotic acid (498-94-2) + glycine (56-40-6) + pipecolic Acid (4043-87-2) + nipecotic acid (498-95-3)

Conditions	Yield
In water at 10 - 20℃; for 1h; contact glow discharge electrolysis (500-600 V, 45 mA);	A 4.3% B 0.1% C 0.8% D 2.9%

pyridine-4-carboxylic acid (55-22-1) → isonipecotic acid (498-94-2)

Conditions	Yield
With i-Amyl alcohol; sodium
With acetic acid; platinum at 40℃; under 2280 Torr; Hydrogenation;
With acetic acid; platinum Hydrogenation;

4-bromo-2-(2-bromo-ethyl)-butyric acid ethyl ester (857778-39-3) → isonipecotic acid (498-94-2)

Conditions	Yield
With ammonia at 130 - 140℃;

2,6-dichloropyridine-4-carboxylic acid (5398-44-7) → isonipecotic acid (498-94-2)

Conditions	Yield
With acetic acid; platinum Hydrogenation;
Multi-step reaction with 2 steps 1: Raney nickel; aqueous NaOH / Hydrogenation.unter Druck 2: platinum; acetic acid / Hydrogenation View Scheme

N-nitroso-isonipecotic acid (6238-69-3, 67659-29-4, 67659-30-7) → isonipecotic acid (498-94-2)

Conditions	Yield
With perchloric acid; ammonium sulfamate; sodium thiocyanide at 50℃; Rate constant; piperidinium perchlorate, 18h; transnitrosating studies;

Piperidine-4-carboxylic acid 4-nitro-phenyl ester; hydrobromide → isonipecotic acid (498-94-2) + 4-nitro-phenol (100-02-7)

Conditions	Yield
With Cu complex of polymer from 2,6-bis-aminomethylpyridine and 4,4'-bis-aminomethyldiphenylmethane; water In dimethyl sulfoxide at 25℃; Rate constant; var.reag.: Cu(2+) complex of 2,6-bis-benzylaminomethylpyridine; oligomers of 2,6-bis-aminomethylpyridine and 4,4'-bis-aminomethyldiphenylmethane;

pyridine-4-carboxylic acid (55-22-1) + acetic acid (64-19-7) + platinum → isonipecotic acid (498-94-2)

Conditions	Yield
Hydrogenation;

pyridine-4-carboxylic acid (55-22-1) + pentan-1-ol (71-41-0) + sodium → isonipecotic acid (498-94-2)

1-benzyloxycarbonylpiperidine-4-carboxylic acid (10314-98-4) → isonipecotic acid (498-94-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: (COCl)2 / toluene; dimethylformamide / 16 h / 18 °C 2: H2, DIEA, thioanisole / Pd/C / toluene / 22 h / 20 °C / 2068.6 Torr View Scheme

Piperidine-1,4-dicarboxylic acid 1-allyl ester 4-(3-methyl-but-2-enyl) ester → isonipecotic acid (498-94-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: 96 percent / diethylamine / Pd(0) (in situ from Pd(OAc)2 and m.sulfonated triphenylphosphine) / acetonitrile; H2O / 0.33 h / 1 molpercent catalyst 2: 100 percent / diethylamine / Pd(0) (in situ from Pd(OAc)2 and m.sulfonated triphenylphosphine) / acetonitrile; H2O / 0.17 h / 5 molpercent catalyst View Scheme

+ 1-(dimethylcarbamoyl)piperidine-4-carboxylic acid + tetramethylurea (632-22-4)

4-carboxamidopiperidine (39546-32-2) → isonipecotic acid (498-94-2)

Conditions	Yield
With amidase from Cupriavidus necator JMP134; water In aq. phosphate buffer at 30℃; pH=7; Enzymatic reaction; stereoselective reaction;

isonipecotic acid (498-94-2) + benzyl chloroformate (501-53-1) → 1-benzyloxycarbonylpiperidine-4-carboxylic acid (10314-98-4)

Conditions	Yield
With sodium hydrogencarbonate; sodium carbonate In water; acetonitrile at 0 - 20℃; for 2h; pH=10 - 11;	100%
With potassium carbonate In water at 22℃; for 58h;	97%
With sodium hydrogencarbonate In tetrahydrofuran; water at 0 - 20℃;	96%

isonipecotic acid (498-94-2) + 1,2-diamino-benzene (95-54-5) → 2-(4-piperidinyl)-1H-benzimidazole (38385-95-4)

Conditions	Yield
Stage #1: isonipecotic acid; 1,2-diamino-benzene at 190℃; for 14h; Stage #2: isonipecotic acid; 1,2-diamino-benzene With phosphoric acid	100%
With PPA at 100℃; for 2h;	92%
With PPA at 180℃; for 2h;	85%

isonipecotic acid (498-94-2) + di-tert-butyl dicarbonate (24424-99-5) → N-[(tert-butoxy)carbonyl]piperidine-4-carboxylic acid (84358-13-4)

Conditions	Yield
In dichloromethane	100%
In sodium hydroxide; tert-butyl alcohol	100%
In sodium hydroxide; tert-butyl alcohol	100%

isonipecotic acid (498-94-2) + N-benzhydryl 3-azetidinone (40320-60-3) → 1-[1-(diphenylmethyl)azetidin-3-yl]piperidine-4-carboxylic acid (874800-95-0)

Conditions	Yield
With methanol; polymer-bound trimethyl ammonium cyanoborohydride; acetic acid at 120℃; for 0.0833333h; Polystyrene; Microwave irradiation;	100%

isonipecotic acid (498-94-2) + phenyl chloroformate (1885-14-9) → 1-benzyloxycarbonylpiperidine-4-carboxylic acid (10314-98-4)

Conditions	Yield
With sodium hydroxide In water at 0 - 25℃; for 18h;	100%

isonipecotic acid (498-94-2) + 1-[3-chloro-5-(5-ethyl-1,2,4-oxadiazol-3-yl)pyridin-2-yl]piperazine bis(trifluoroacetate) → 1-(3-cyano-5-(isopropoxycarbonyl)-6-methylpyridin-2-yl)piperidine-4-carboxylic acid (898227-66-2)

Conditions	Yield
Stage #1: isonipecotic acid; 1-[3-chloro-5-(5-ethyl-1,2,4-oxadiazol-3-yl)pyridin-2-yl]piperazine bis(trifluoroacetate) With N-ethyl-N,N-diisopropylamine In ethanol for 1h; Heating / reflux; Stage #2: With potassium hydrogensulfate In ethanol; water at 20℃;	100%

isonipecotic acid (498-94-2) + 2-chloro-5-(5-ethyl-1,3-oxazol-2-yl)-6-methylnicotinonitrile (898229-16-8) → 1-[3-cyano-5-(5-ethyl-1,3-oxazol-2-yl)-6-methylpyridin-2-yl]piperidine-4-carboxylic acid (898229-21-5)

Conditions	Yield
at 120℃; for 0.666667h; Microwave irradiation;	100%

isonipecotic acid (498-94-2) + isopropyl 6-chloro-3-cyano-2-methylnicotinate (898227-65-1) → 1-(3-cyano-5-(isopropoxycarbonyl)-6-methylpyridin-2-yl)piperidine-4-carboxylic acid (898227-66-2)

Conditions	Yield
Stage #1: isonipecotic acid; isopropyl 6-chloro-3-cyano-2-methylnicotinate With N-ethyl-N,N-diisopropylamine In ethanol for 1h; Heating / reflux; Stage #2: With potassium hydrogensulfate In ethanol; water at 20℃;	100%
Stage #1: isonipecotic acid; isopropyl 6-chloro-3-cyano-2-methylnicotinate With N-ethyl-N,N-diisopropylamine In ethanol for 1h; Heating / reflux; Stage #2: With potassium hydrogensulfate In ethanol; water	100%

isonipecotic acid (498-94-2) + 1,3,5-trichloro-2,4,6-triazine (108-77-0) + methylamine (74-89-5) → 1-[4-methyl-6-(methylamino)-1,3,5-triazin-2-yl]-4-piperidinecarboxylicacid (1141894-74-7)

Conditions	Yield
Stage #1: 1,3,5-trichloro-2,4,6-triazine; methylamine With sodium hydroxide In water; acetonitrile at 0℃; for 0.5h; pH=9 - 10; Stage #2: isonipecotic acid In water; acetonitrile at 0 - 20℃; for 1h; pH=9 - 10;	100%

isonipecotic acid (498-94-2) + 4-(chloromethyl)-2-(4-fluorophenyl)-5-methyl-1,3-oxazole (625826-69-9) → 1-((2-(4-fluorophenyl)-5-methyloxazol-4-yl)methyl)piperidine-4-carboxylic acid

Conditions	Yield
With potassium hydroxide In ethanol at 20℃; for 16h;	100%

isonipecotic acid (498-94-2) + 4-(chloromethyl)-5-methyl-2-(2,6-difluorophenyl)oxazole → 1-((2-(2,6-difluorolphenyl)-5-methyloxazol-4-yl)methyl)piperidine-4-carboxylic acid

Conditions	Yield
With potassium hydroxide In ethanol at 20℃; for 16h;	100%

isonipecotic acid (498-94-2) + 4-(chloromethyl)-5-methyl-2-(2,6-dibromophenyl)oxazole → 1-((2-(2,6-dibromophenyl)-5-methyloxazol-4-yl)methyl)piperidine-4-carboxylic acid

Conditions	Yield
With potassium hydroxide In ethanol at 20℃; for 16h;	100%

isonipecotic acid (498-94-2) + 4-(chloromethyl)-5-methyl-2-(2-fluoro-6-methylphenyl)oxazole → 1-((2-(2-fluoro-6-methylphenyl)-5-methyloxazol-4-yl)methyl)piperidine-4-carboxylic acid

Conditions	Yield
With potassium hydroxide In ethanol at 20℃; for 16h;	100%

isonipecotic acid (498-94-2) + 4-(chloromethyl)-5-methyl-2-(2-methoxy-6-methylphenyl)oxazole → 1-((2-(2-methoxy-6-methylphenyl)-5-methyloxazol-4-yl)methyl)piperidine-4-carboxylic acid

Conditions	Yield
With potassium hydroxide In ethanol at 20℃; for 16h;	100%

isonipecotic acid (498-94-2) + 4-(5-chlorosulfonyl-2-n-propoxybenzamido)-1-methyl-3-n-propylpyrazole-5-carboxamide (374776-34-8) → 4-(5-(4-(hydroxycarbonyl)piperidinylsulfonyl)-2-n-propoxybenzamido)-1-methyl-3-n-propylpyrazole-5-carboxamide

Conditions	Yield
With triethylamine In ethanol at 20℃; for 2h;	99%

isonipecotic acid (498-94-2) + ethanol (64-17-5) → piperidine-4-carboxylic acid ethyl ester hydrochloride

Conditions	Yield
With thionyl chloride for 3.83333h; Cooling with ice; Reflux;	99%
With thionyl chloride at 0℃; for 3h; Reflux;	96%
Stage #1: isonipecotic acid; ethanol With thionyl chloride at 0℃; for 3h; Heating / reflux; Stage #2: With hydrogenchloride In ethanol	90.2%
With thionyl chloride at 0 - 90℃; for 6h;	80.05%
With thionyl chloride Inert atmosphere; Reflux;

isonipecotic acid (498-94-2) + copper(II) perchlorate hexahydrate → [Cu(piperidine-4-carboxylic acid)4][ClO4]2

Conditions	Yield
In water soln. of metal compd. added to aq. soln. of ligand (1:4), stirred at 70°C for 10 min; crystd. on storage for several h, elem. anal.;	99%

isonipecotic acid (498-94-2) + 4-(chloromethyl)-5-methyl-2-(2,6-dichlorophenyl)oxazole → 1-((2-(2,6-dichlorophenyl)-5-methyloxazol-4-yl)methyl)piperidine-4-carboxylic acid

Conditions	Yield
With potassium hydroxide In ethanol at 20℃; for 16h;	99%

isonipecotic acid (498-94-2) + 4-(chloromethyl)-5-methyl-2-(2-fluoro-6-methoxyphenyl)oxazole → 1-((2-(2-fluoro-6-methoxyphenyl)-5-methyloxazol-4-yl)methyl)piperidine-4-carboxylic acid

Conditions	Yield
With potassium hydroxide In ethanol at 20℃; for 16h;	99%

Upstream product

• 4989-37-1 [p-(Phenylazo)phenyl]thiourea 
• 4989-36-0 4-(AMINOCARBONOTHIOYL)BENZOIC ACID 
• 4988-89-0 1,1',1''-(1,3,5-triazine-2,4,6-triyltriimino)trisanthraquinone 
• 4988-84-5 (22S,23R,25R)-23-Bromo-5α-spirostane 
• 4988-66-3 2-bromo-N-(2-chloroethyl)-N-(3,5-dimethoxybenzyl)ethanamine 
• 4988-64-1 6-MERCAPTOPURINE RIBOSIDE 
• 4988-44-7 2,4-dichloro-6-nitrophenyl 2-ethylhexanoate 
• 498-83-9 4-BroMobenzenesulfonyl fluoride 
• 4988-34-5 Pentamethylene 
• 4988-33-4 tetrahydro-2H-thiopyran 1,1-dioxide 
• 4988-32-3 4-[(4-amino-3-bromo-9,10-dihydro-9,10-dioxo-1-anthryl)amino]toluene-3-sulphonic acid 
• 4988-30-1 disodium 3-[[2-(acetylamino)-4-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]phenyl]azo]naphthalene-1,5-disulphonate 
• 4988-26-5 acetyltanghinin 
• 4988-24-3 4-Methyl-19-norspirosta-1,3,5(10)-triene 

Downstream Products

• 25503-90-6 1-Acetyl-4-piperidinecarboxylic acid 
• 25519-79-3 1-ACETYL-4-BENZOYLPIPERIDINE 
• 91419-52-2 1-Boc-4-cyanopiperidine 
• 59084-16-1 1-ACETYLISONIPECOTOYL CHLORIDE 
• 31252-42-3 4-BENZYLPIPERIDINE 
• 73874-95-0 4-N-BOC-Aminopiperidine 
• 174316-71-3 N-BOC-ISONIPECOTIC ACID 
• 10314-98-4 1-[(Benzyloxy)carbonyl]piperidine-4-carboxylic acid 
• 135632-53-0 4-(Boc-Aminomethyl)piperidine 
• 137076-22-3 1-tert-Butoxycarbonyl-4-piperidinecarboxaldehyde 
• 144222-22-0 1-Boc-4-(aminomethyl)piperidine 
• 159275-17-9 BENZYL 4-(BROMOMETHYL)TETRAHYDRO-1(2H)-PYRIDINECARBOXYLATE 
• 162368-01-6 1-(4-ACETYLPIPERIDINO)ETHAN-1-ONE 
• 41838-46-4 1-Methylpiperidin-4-amine 
• 4395-98-6 4-Cyanopiperidine 
• 63214-58-4 1-(PIPERIDIN-4-YLCARBONYL)PIPERIDINE 
• 68947-43-3 1-METHYL-PIPERIDINE-4-CARBOXYLIC ACID 
• 71985-80-3 1-METHYLPIPERIDINE-4-CARBOXYLIC ACID HYDROCHLORIDE 
• 84163-77-9 6-Fluoro-3-(4-piperidinyl)-1,2-benzisoxazole 
• 84358-13-4 N-BOC-piperidine-4-carboxylic acid 
• 892493-65-1 4-PIPERIDINECARBOXYLIC ACID T-BUTYL ESTER HCL 

Recommend Products

• 100957-76-4  1-indol-3-ylmethyl-piperidine-4-carboxylic acid 
• 120-72-9  indole 
• 50-00-0  formaldehyd 
• 55-22-1  pyridine-4-carboxylic acid 
• 857778-39-3  4-bromo-2-(2-bromo-ethyl)-butyric acid ethyl ester 
• 5398-44-7  2,6-dichloropyridine-4-carboxylic acid 
• 51784-03-3  4-(benzoxazol-2-yl)piperidine 
• 95-55-6  2-amino-phenol 
• 51784-73-7  4-(benzothiazol-2-yl)-piperidine 
• 137-07-5  2-amino-benzenethiol 
• 138163-08-3  N-(benzyloxycarbonyl)piperidine-4-carboxaldehyde 
• 10314-99-5  benzyl 4-(chlorocarbonyl)piperidine-1-carboxylate 
• 208987-65-9  (2S,4S)-4-Acetylsulfanyl-2-amino-pyrrolidine-1-carboxylic acid 4-nitro-benzyl ester 
• 2971-79-1  isonipecotic acid methyl ester