74892-82-3

Basic information

• Product Name: Ethyl (2R,4R)-4-methyl-2-piperidinecarboxylate
• Synonyms: ethyl (2r,4r)-4-methyl-2-piperidinecarboxylate;(2R,4R)-4-METHYL-2-PIPERIDINECARBOXYLATE;(2R,4R)4-methylpiperidecarboxylicacid;(2R,4R)-ETHYL 4-METHYLPIPERIDINE-2-CARBOXYLATE;(2R,4R)-4-Methyl-2-piperidinecarboxylic Acid Ethyl Ester;(2R-trans)-4-Methyl-2-piperidinecarboxylic Acid Ethyl Ester;Ethyl (2R,4R)-4-Methylpipecolate;ethyl (2R,4R)-4-Methylpiperidine-2-carboxylate
• CAS NO: 74892-82-3
• Molecular Formula: C₉H₁₇NO₂
• Molecular Weight: 171.24
• EINECS: 1806241-263-5
• Product Categories: Chiral Reagents;Heterocycles;Intermediates & Fine Chemicals;Pharmaceuticals;Heterocycle-other series
• Mol File: 74892-82-3.mol
• Article Data: 6

Chemical Properties

• Boiling Point: 226.1 °C at 760 mmHg
• Flash Point: 90.5 °C
• Appearance: /
• Density: 0.969 g/cm³
• Vapor Pressure: 0.0835mmHg at 25°C
• Refractive Index: 1.441
• Storage Temp.: Keep in dark place,Sealed in dry,Store in freezer, under -20°C
• PKA: 6.65±0.10(Predicted)
• CAS DataBase Reference: Ethyl (2R,4R)-4-methyl-2-piperidinecarboxylate(CAS DataBase Reference)
• NIST Chemistry Reference: Ethyl (2R,4R)-4-methyl-2-piperidinecarboxylate(74892-82-3)
• EPA Substance Registry System: Ethyl (2R,4R)-4-methyl-2-piperidinecarboxylate(74892-82-3)

Safety Data

• Hazardous Substances Data: 74892-82-3(Hazardous Substances Data)

Usage

Chemical Properties

light yellow solution

Uses

Ethyl (2R,4R)-4-Methylpipecolate is an intermediate in the preparation of Argatroban (A769000).

InChI:InChI=1/C9H17NO2/c1-3-12-9(11)8-6-7(2)4-5-10-8/h7-8,10H,3-6H2,1-2H3/t7-,8-/m1/s1

Synthetic route

ethyl (2R,4R)-4-methyl-2-piperidinecarboxylate L-(+)-tartarate (131278-84-7) → ethyl (2R-trans)-4-methylpiperidine-2-carboxylate (74892-82-3)

Conditions	Yield
With potassium carbonate In water; ethyl acetate at 15 - 20℃; for 1h;	88%

ethyl (2R,4R)-4-methyl-1-((S)-1-phenylethyl)tetrahydropyridine-2-carboxylate (198641-56-4) → ethyl (2R-trans)-4-methylpiperidine-2-carboxylate (74892-82-3)

Conditions	Yield
With 10% palladium hydroxide on charcoal; hydrogen In ethanol at 20℃; under 760.051 Torr; for 4h;	45%
With palladium 10% on activated carbon; hydrogen; iron(II) oxalate; acetic acid In ethanol at 30℃; under 3750.38 Torr; for 4h; Reagent/catalyst; Autoclave;	345 g

(2R,4R)-4-Methyl-1-((R)-1-phenyl-ethyl)-piperidine-2-carboxylic acid ethyl ester (134984-62-6, 134984-77-3) → ethyl (2R-trans)-4-methylpiperidine-2-carboxylate (74892-82-3)

Conditions	Yield
With hydrogen; palladium hydroxide - carbon In ethanol under 760 Torr; Ambient temperature;

(6R)-1-<(R)-1-phenylethyl>-6-ethoxycarbonyl-4-methyl-3,4-didehydropiperidine (139334-62-6) → ethyl (2R-trans)-4-methylpiperidine-2-carboxylate (74892-82-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: H2 / 3percent Pt-C / ethyl acetate / 16 h / 760 Torr / Ambient temperature 2: H2 / Pd(OH)2-C / ethanol / 760 Torr / Ambient temperature View Scheme

isoprene (78-79-5) → ethyl (2R-trans)-4-methylpiperidine-2-carboxylate (74892-82-3)

Conditions	Yield
Multi-step reaction with 3 steps 1: TFA, H2O / dimethylformamide / 30 h / Ambient temperature 2: H2 / 3percent Pt-C / ethyl acetate / 16 h / 760 Torr / Ambient temperature 3: H2 / Pd(OH)2-C / ethanol / 760 Torr / Ambient temperature View Scheme

ethyl (2R)-4-methyl-1-((S)-1-phenylethyl)-1,2,3,6-tetrahydropyridine-2-carboxylate (139334-63-7) → ethyl (2R-trans)-4-methylpiperidine-2-carboxylate (74892-82-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: (SP, S′P)-1,1′-bis[bis(4-methoxy-3,5-dimethylphenyl)phosphino]-2,2′-bis[(R)-α-(dimethylamino)benzyl]ferrocene; bis(norbornadiene)rhodium(l)tetrafluoroborate; methanesulfonic acid; hydrogen / ethanol / 18 h / 90 °C / 7500.75 Torr / Autoclave 2: 10% palladium hydroxide on charcoal; hydrogen / ethanol / 4 h / 20 °C / 760.05 Torr View Scheme
Multi-step reaction with 2 steps 1: 3 % platinum on carbon; hydrogen / ethyl acetate / 48 h / 20 °C / 760.05 Torr 2: 10% palladium hydroxide on charcoal; hydrogen / ethanol / 4 h / 20 °C / 760.05 Torr View Scheme

ethyl 4-methyl-2-piperidinecarboxylate L-tartrate → ethyl (2R-trans)-4-methylpiperidine-2-carboxylate (74892-82-3)

Conditions	Yield
With potassium carbonate In water; ethyl acetate at 20℃; for 1h;

4-methylpiperidin (626-58-4) → ethyl (2R-trans)-4-methylpiperidine-2-carboxylate (74892-82-3)

Conditions

Yield

Multi-step reaction with 7 steps 1.1: acetic acid; sodium hypochlorite / water / 2 h / 0 - 10 °C 1.2: 0 - 20 °C 2.1: hydrogenchloride / water; dichloromethane / 1.5 h / 0 - 10 °C 3.1: water; dichloromethane / 0 - 20 °C 4.1: hydrogenchloride / water / 20 - 60 °C 5.1: thionyl chloride / 0 °C / Reflux 6.1: ethanol; acetone / 0.5 h / 40 °C / Resolution of racemate 7.1: potassium carbonate / water; ethyl acetate / 1 h / 15 - 20 °C View Scheme

2,3,4,5-tetrahydro-4-methylpyridine (85796-64-1) → ethyl (2R-trans)-4-methylpiperidine-2-carboxylate (74892-82-3)

Conditions	Yield
Multi-step reaction with 6 steps 1: hydrogenchloride / water; dichloromethane / 1.5 h / 0 - 10 °C 2: water; dichloromethane / 0 - 20 °C 3: hydrogenchloride / water / 20 - 60 °C 4: thionyl chloride / 0 °C / Reflux 5: ethanol; acetone / 0.5 h / 40 °C / Resolution of racemate 6: potassium carbonate / water; ethyl acetate / 1 h / 15 - 20 °C View Scheme

4-methyl-2,3,4,5-tetrahydropyridine hydrochloride → ethyl (2R-trans)-4-methylpiperidine-2-carboxylate (74892-82-3)

Conditions	Yield
Multi-step reaction with 5 steps 1: water; dichloromethane / 0 - 20 °C 2: hydrogenchloride / water / 20 - 60 °C 3: thionyl chloride / 0 °C / Reflux 4: ethanol; acetone / 0.5 h / 40 °C / Resolution of racemate 5: potassium carbonate / water; ethyl acetate / 1 h / 15 - 20 °C View Scheme

4-methyl-2-piperidinecarbonitrile → ethyl (2R-trans)-4-methylpiperidine-2-carboxylate (74892-82-3)

Conditions	Yield
Multi-step reaction with 4 steps 1: hydrogenchloride / water / 20 - 60 °C 2: thionyl chloride / 0 °C / Reflux 3: ethanol; acetone / 0.5 h / 40 °C / Resolution of racemate 4: potassium carbonate / water; ethyl acetate / 1 h / 15 - 20 °C View Scheme

ethyl 4-methyl-2-piperidinecarboxylate L-tartrate → ethyl (2R-trans)-4-methylpiperidine-2-carboxylate (74892-82-3) + ethyl (2S,4S)-4-methylpiperidine-2-carboxylate (78306-52-2)

Conditions	Yield
With potassium carbonate In water; ethyl acetate at 15 - 20℃; for 1.08333h; Overall yield = 85 %; Overall yield = 29.4 g;	A n/a B n/a

ethyl trans-(±)-4-methylpiperidine-2-carboxylate → ethyl (2R-trans)-4-methylpiperidine-2-carboxylate (74892-82-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: ethanol; acetone / 0.5 h / 40 °C / Resolution of racemate 2: potassium carbonate / water; ethyl acetate / 1 h / 15 - 20 °C View Scheme

trans-(±)-4-methylpiperidine-2-carboxylic acid hydrochloride → ethyl (2R-trans)-4-methylpiperidine-2-carboxylate (74892-82-3)

Conditions	Yield
Multi-step reaction with 3 steps 1: thionyl chloride / 0 °C / Reflux 2: ethanol; acetone / 0.5 h / 40 °C / Resolution of racemate 3: potassium carbonate / water; ethyl acetate / 1 h / 15 - 20 °C View Scheme

1,2,3,4-tetrahydro-3-methyl-8-quinolinesulfonyl chloride (153886-63-6) + N-Boc-N'-nitro-L-arginine + ethyl (2R-trans)-4-methylpiperidine-2-carboxylate (74892-82-3) → (2R,4R)-1-[NG-nitro-N2-(3-methyl-8-quinolinesulfonyl)-L-arginyl]-4-methyl-2-piperidinecarboxylic acid ethyl ester

Conditions	Yield
Stage #1: N-Boc-N'-nitro-L-arginine; ethyl (2R-trans)-4-methylpiperidine-2-carboxylate With 4-methyl-morpholine; 2-chloro-4,6-dimethoxy-1 ,3,5-triazine In chloroform at -30℃; for 2h; Stage #2: 1,2,3,4-tetrahydro-3-methyl-8-quinolinesulfonyl chloride In chloroform at 20℃; for 3h; Temperature;	87.5%

Boc-Orn(Z)-OH (2480-93-5) + ethyl (2R-trans)-4-methylpiperidine-2-carboxylate (74892-82-3) → (2R,4R)-1-((S)-5-Benzyloxycarbonylamino-2-tert-butoxycarbonylamino-pentanoyl)-4-methyl-piperidine-2-carboxylic acid ethyl ester (174699-01-5)

Conditions	Yield
With 4-methyl-morpholine; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 20℃; for 0.75h; Acylation;	86%

ethyl (2R-trans)-4-methylpiperidine-2-carboxylate (74892-82-3) + 5-benzyloxycarbonylamino-2-tert-butoxycarbonylamino-4,4-difluoro-pentanoic acid (183679-12-1) → (2R,4R)-1-((S)-5-Benzyloxycarbonylamino-2-tert-butoxycarbonylamino-4,4-difluoro-pentanoyl)-4-methyl-piperidine-2-carboxylic acid ethyl ester (183679-13-2)

Conditions	Yield
With 4-methyl-morpholine; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 0 - 20℃; Acylation;	84%

ethyl (2R-trans)-4-methylpiperidine-2-carboxylate (74892-82-3) + (S)-4-(1,3-Dioxo-1,3-dihydro-isoindol-2-yloxy)-2-(3-methyl-1,2,3,4-tetrahydro-quinoline-8-sulfonylamino)-butyric acid (183679-09-6) → (2R,4R)-1-[(S)-4-(1,3-Dioxo-1,3-dihydro-isoindol-2-yloxy)-2-(3-methyl-1,2,3,4-tetrahydro-quinoline-8-sulfonylamino)-butyryl]-4-methyl-piperidine-2-carboxylic acid ethyl ester

Conditions	Yield
With 4-methyl-morpholine; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 0 - 20℃; Acylation;	79%

N2-(3-methyl-8-quinolinesulfonyl)-NG-nitro-L-arginine + ethyl (2R-trans)-4-methylpiperidine-2-carboxylate (74892-82-3) → (2R,4R)-1-[NG-nitro-N2-(3-methyl-8-quinolinesulfonyl)-L-arginyl]-4-methyl-2-piperidinecarboxylic acid ethyl ester

Conditions	Yield
Stage #1: N2-(3-methyl-8-quinolinesulfonyl)-NG-nitro-L-arginine With trichlorophosphate In tetrahydrofuran at -30℃; for 2h; Reflux; Stage #2: ethyl (2R-trans)-4-methylpiperidine-2-carboxylate In tetrahydrofuran for 2h;	72.6%

Boc-Asp(OtBu)-OH (1676-90-0) + ethyl (2R-trans)-4-methylpiperidine-2-carboxylate (74892-82-3) → (2R,4R)-1-((S)-3-tert-Butoxycarbonyl-2-tert-butoxycarbonylamino-propionyl)-4-methyl-piperidine-2-carboxylic acid ethyl ester

Conditions	Yield
With N-ethylmorpholine;; (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate In N,N-dimethyl-formamide

ethyl (2R-trans)-4-methylpiperidine-2-carboxylate (74892-82-3) → (2R,4R)-1-((S)-2-Amino-5-benzyloxycarbonylamino-pentanoyl)-4-methyl-piperidine-2-carboxylic acid ethyl ester (174699-02-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: 86 percent / 1-ethyl-3-(3-dimethylamino)propyl carbodiimide hydrochloride; HOBt; 4-methylmorpholine / dimethylformamide / 0.75 h / 20 °C 2: 100 percent / TFA / 1 h / 0 - 20 °C View Scheme

ethyl (2R-trans)-4-methylpiperidine-2-carboxylate (74892-82-3) → (2R,4R)-1-[(S)-5-Amino-2-(3-methyl-1,2,3,4-tetrahydro-quinoline-8-sulfonylamino)-pentanoyl]-4-methyl-piperidine-2-carboxylic acid ethyl ester

Conditions	Yield
Multi-step reaction with 4 steps 1: 86 percent / 1-ethyl-3-(3-dimethylamino)propyl carbodiimide hydrochloride; HOBt; 4-methylmorpholine / dimethylformamide / 0.75 h / 20 °C 2: 100 percent / TFA / 1 h / 0 - 20 °C 3: 75 percent / Et3N / CH2Cl2 / 2.75 h / 20 °C 4: 92 percent / H2 / Pd black / ethanol / 72 h / 760 Torr View Scheme

ethyl (2R-trans)-4-methylpiperidine-2-carboxylate (74892-82-3) → (2R,4R)-1-[(S)-5-Cyanoamino-2-(3-methyl-1,2,3,4-tetrahydro-quinoline-8-sulfonylamino)-pentanoyl]-4-methyl-piperidine-2-carboxylic acid ethyl ester

Conditions	Yield
Multi-step reaction with 5 steps 1: 86 percent / 1-ethyl-3-(3-dimethylamino)propyl carbodiimide hydrochloride; HOBt; 4-methylmorpholine / dimethylformamide / 0.75 h / 20 °C 2: 100 percent / TFA / 1 h / 0 - 20 °C 3: 75 percent / Et3N / CH2Cl2 / 2.75 h / 20 °C 4: 92 percent / H2 / Pd black / ethanol / 72 h / 760 Torr 5: 100 percent / NH4OAc / methanol / 24 h / 20 °C View Scheme

ethyl (2R-trans)-4-methylpiperidine-2-carboxylate (74892-82-3) → C25H40N6O6S

Conditions

Yield

Multi-step reaction with 6 steps 1: 86 percent / 1-ethyl-3-(3-dimethylamino)propyl carbodiimide hydrochloride; HOBt; 4-methylmorpholine / dimethylformamide / 0.75 h / 20 °C 2: 100 percent / TFA / 1 h / 0 - 20 °C 3: 75 percent / Et3N / CH2Cl2 / 2.75 h / 20 °C 4: 92 percent / H2 / Pd black / ethanol / 72 h / 760 Torr 5: 100 percent / NH4OAc / methanol / 24 h / 20 °C 6: 40 percent / H2NOH / methanol / 2 h / 20 °C View Scheme

ethyl (2R-trans)-4-methylpiperidine-2-carboxylate (74892-82-3) → (2R,4R)-1-[(S)-5-Benzyloxycarbonylamino-2-(3-methyl-quinoline-8-sulfonylamino)-pentanoyl]-4-methyl-piperidine-2-carboxylic acid ethyl ester (174699-04-8)

Conditions	Yield
Multi-step reaction with 3 steps 1: 86 percent / 1-ethyl-3-(3-dimethylamino)propyl carbodiimide hydrochloride; HOBt; 4-methylmorpholine / dimethylformamide / 0.75 h / 20 °C 2: 100 percent / TFA / 1 h / 0 - 20 °C 3: 75 percent / Et3N / CH2Cl2 / 2.75 h / 20 °C View Scheme

ethyl (2R-trans)-4-methylpiperidine-2-carboxylate (74892-82-3) → (2R,4R)-1-((S)-2-Amino-3-tert-butoxycarbonyl-propionyl)-4-methyl-piperidine-2-carboxylic acid ethyl ester

Conditions	Yield
Multi-step reaction with 2 steps 1: 4-ethylmorpholine, (benzotriazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate / dimethylformamide 2: p-toluenesulfonic acid monohydrate / acetonitrile / 8 h / Ambient temperature View Scheme

ethyl (2R-trans)-4-methylpiperidine-2-carboxylate (74892-82-3) → (2R,4R)-1-[(S)-3-Carboxy-2-(naphthalene-2-sulfonylamino)-propionyl]-4-methyl-piperidine-2-carboxylic acid ethyl ester (1027984-73-1)

Conditions	Yield
Multi-step reaction with 4 steps 1: 4-ethylmorpholine, (benzotriazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate / dimethylformamide 2: p-toluenesulfonic acid monohydrate / acetonitrile / 8 h / Ambient temperature 3: aq. NaHCO3 / dioxane 4: HCl / ethyl acetate / 5 h / Ambient temperature View Scheme

ethyl (2R-trans)-4-methylpiperidine-2-carboxylate (74892-82-3) → (2R,4R)-1-[(S)-3-tert-Butoxycarbonyl-2-(naphthalene-2-sulfonylamino)-propionyl]-4-methyl-piperidine-2-carboxylic acid ethyl ester (1027037-83-7)

Conditions	Yield
Multi-step reaction with 3 steps 1: 4-ethylmorpholine, (benzotriazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate / dimethylformamide 2: p-toluenesulfonic acid monohydrate / acetonitrile / 8 h / Ambient temperature 3: aq. NaHCO3 / dioxane View Scheme

ethyl (2R-trans)-4-methylpiperidine-2-carboxylate (74892-82-3) → (2R,4R)-1-[(S)-3-[((S)-1-Carbamimidoyl-piperidin-3-ylmethyl)-carbamoyl]-2-(naphthalene-2-sulfonylamino)-propionyl]-4-methyl-piperidine-2-carboxylic acid ethyl ester

Conditions

Yield

Multi-step reaction with 5 steps 1: 4-ethylmorpholine, (benzotriazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate / dimethylformamide 2: p-toluenesulfonic acid monohydrate / acetonitrile / 8 h / Ambient temperature 3: aq. NaHCO3 / dioxane 4: HCl / ethyl acetate / 5 h / Ambient temperature 5: 4-ethylmorpholine, (benzotriazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate / dimethylformamide View Scheme

ethyl (2R-trans)-4-methylpiperidine-2-carboxylate (74892-82-3) → ethyl (2R,4R)-1-[(2S)-2-[[(1,1-dimethyletoxy)carbonyl]amino]-5-[[imino(nitroamino)methyl]amino]-1-oxopentyl]-4-methylpiperidine-2-carboxylate (74874-07-0)

Conditions	Yield
Stage #1: ethyl (2R-trans)-4-methylpiperidine-2-carboxylate With 4-methyl-morpholine; 2-chloro-4,6-dimethoxy-1 ,3,5-triazine In ethyl acetate at -10℃; for 1.5h; Stage #2: ethyl (2R-trans)-4-methylpiperidine-2-carboxylate In ethyl acetate at -10 - 10℃;

Boc-Arg(NO2)-OH (2188-18-3) + ethyl (2R-trans)-4-methylpiperidine-2-carboxylate (74892-82-3) → ethyl (2R,4R)-1-[(2S)-2-[[(1,1-dimethylethoxy)carbonyl]amino]-5-[[imino(nitroamino)methyl]amino]-1-oxopentyl]-4-methylpiperidine-2-carboxylate (74874-07-0)

Conditions	Yield
Stage #1: Boc-Arg(NO2)-OH With 4-methyl-morpholine; 2-chloro-4,6-dimethoxy-1 ,3,5-triazine In ethyl acetate at -10 - -5℃; for 1.5h; Stage #2: ethyl (2R-trans)-4-methylpiperidine-2-carboxylate In ethyl acetate at -5 - 10℃;	85 g

Boc-Arg(NO2)-OH (2188-18-3) + ethyl (2R-trans)-4-methylpiperidine-2-carboxylate (74892-82-3) → ethyl (2R,4R)-1-[(2S)-2-amino-5-[[imino(nitroamino)methyl]amino]-1-oxopentyl]-4-methylpiperidine-2-carboxylate dihydrochloride

Conditions	Yield
Multi-step reaction with 2 steps 1.1: 2-chloro-4,6-dimethoxy-1 ,3,5-triazine; 4-methyl-morpholine / ethyl acetate / 1.5 h / -10 - -5 °C 1.2: -5 - 10 °C 2.1: hydrogenchloride / ethanol / 15 - 20 °C View Scheme

Upstream product

• 42205-75-4 ethyl trans-(±)-4-methylpiperidine-2-carboxylate 
• 131278-84-7 ethyl (2R,4R)-4-methyl-2-piperidinecarboxylate L-(+)-tartarate 
• 85796-64-1 2,3,4,5-tetrahydro-4-methylpyridine 
• 626-58-4 4-methylpiperidin 
• 198641-56-4 ethyl (2R,4R)-4-methyl-1-((S)-1-phenylethyl)tetrahydropyridine-2-carboxylate 
• 139334-63-7 ethyl (2R)-4-methyl-1-((S)-1-phenylethyl)-1,2,3,6-tetrahydropyridine-2-carboxylate 
• 78-79-5 isoprene 
• 139334-62-6 (6R)-1-<(R)-1-phenylethyl>-6-ethoxycarbonyl-4-methyl-3,4-didehydropiperidine 
• 134984-62-6 (2R,4R)-4-Methyl-1-((R)-1-phenyl-ethyl)-piperidine-2-carboxylic acid ethyl ester 

Downstream Products

• 183679-13-2 (2R,4R)-1-((S)-5-Benzyloxycarbonylamino-2-tert-butoxycarbonylamino-4,4-difluoro-pentanoyl)-4-methyl-piperidine-2-carboxylic acid ethyl ester 
• 74874-07-0 ethyl (2R,4R)-1-[(2S)-2-[[(1,1-dimethyletoxy)carbonyl]amino]-5-[[imino(nitroamino)methyl]amino]-1-oxopentyl]-4-methylpiperidine-2-carboxylate 
• 74874-07-0 ethyl (2R,4R)-1-[(2S)-2-[[(1,1-dimethylethoxy)carbonyl]amino]-5-[[imino(nitroamino)methyl]amino]-1-oxopentyl]-4-methylpiperidine-2-carboxylate 
• 174699-04-8 (2R,4R)-1-[(S)-5-Benzyloxycarbonylamino-2-(3-methyl-quinoline-8-sulfonylamino)-pentanoyl]-4-methyl-piperidine-2-carboxylic acid ethyl ester 
• 174699-02-6 (2R,4R)-1-((S)-2-Amino-5-benzyloxycarbonylamino-pentanoyl)-4-methyl-piperidine-2-carboxylic acid ethyl ester 
• 174699-01-5 (2R,4R)-1-((S)-5-Benzyloxycarbonylamino-2-tert-butoxycarbonylamino-pentanoyl)-4-methyl-piperidine-2-carboxylic acid ethyl ester 

Relevant articles and documents

Synthesis method of argatroban intermediate (2R,4R)-4-methyl piperidine-2-ethyl formate

The invention relates to a synthesis method of an argatroban intermediate (2R,4R)-4-methyl piperidine-2-ethyl formate compound. The synthesis method comprises the following steps: (1) under the action of a rhodium catalyst and ferric oxalate, carrying out catalytic hydrogenation on (2R)-4-methyl-1-((S)-1-phenethyl)-1,2,3,6-tetrahydropyridine-2-ethyl formate, so that (2R,4R)-4-methyl-1-((S)-1-phenethyl)-2-pyridine ethyl formate is obtained; and (2) under the action of a palladium catalyst and ferric oxalate, removing benzyl, so that the (2R,4R)-4-methyl piperidine-2-ethyl formate is obtained. The synthesis method provided by the invention has the advantages that the ferric oxalate is introduced into a reaction system, two-step reaction yield is increased, especially the efficiency is the highest when the ferric oxalate and a rhodium-silicon dioxide catalyst are used together, and the cost is effectively reduced, so that the synthesis method is applicable to industrial production.

METHOD FOR THE PREPARATION OF PROCESS INTERMEDIATES FOR THE SYNTHESIS OF ARGATROBAN MONOHYDRATE

Object of the present invention is a method for the synthesis of a key intermediate for the synthesis of Argatroban monohydrate, ethyl (2R,4R)-1-[(2S)-2-amino-5-[[imino(nitroamino)methyl]amino]-1-oxopentyl]-4- methylpiperidine-2-carboxylate compounded with HCl.

ANTITHROMBOTIC AMIDINOTETRAHYDROPYRIDYLALANINE DERIVATIVES

This invention is directed to compounds of formula (I), STR1 pharmaceutically acceptable salts thereof, and pharmaceutically acceptable solvates of either entity, wherein Y is optionally monounsaturated C 3-C 5 alkylene optionally substituted with C. sub.1-C 4 alkyl or methylene; R 1 is H; C 1-C 4 alkyl optionally substituted with C 1-C 4 alkoxy, OH, NR 5 R 6, CONR 5 R 6, C 3-C 6 cycloalkyl or aryl; or C 3-C 6 alkenyl; R 2 is H; C 1-C 4 alkyl optionally substituted with C 1-C 4 alkoxy, OH, NR 5 R 6, CONR 5 R 6, C 3-C 6 cycloalkyl or aryl; or CONR 5 R 6 ; R. sup.3 and R 4 are each independently selected from H; C 1-C. sub. 4 alkyl optionally substituted with NR 5 R 6 ; C 1-C. sub.4 alkoxy; halo; CONR 5 R 6 and aryl; aryl is phenyl optionally substituted with one, two or three substituents independently selected from C 1-C 4 alkyl, C 1-C 4 alkoxy, OH, halo and CF 3 ; R 5 and R 6 are each independently selected from H and C 1-C 4 alkyl; and m and n are each independently 1, 2 or 3; which are potent and selective thrombin inhibitors useful in the treatment of inter alia, deep vein thrombosis; reocclusion following thrombolytic therapy; chronic arterial obstruction; peripheral vascular disease; acute myocardial infarction; unstable angina; atrial fibrillation; thrombotic stroke; transient ischaemic attacks; restenosis and occlusion following angioplasty; or neurodegenerative disorders.