309956-78-3

Basic information

• Product Name: (R)-3-(Boc-Amino)piperidine
• Synonyms: CARBAMIC ACID, (3R)-3-PIPERIDINYL-, 1,1-DIMETHYLETHYL ESTER;(R)-TERT-BUTYL-PIPERIDINE-3-YICARBAMATE;(R)-PIPERIDIN-3-YL-CARBAMIC ACID TERT-BUTYL ESTER;(R)-3-AMINO-N-TBOC-PIPERIDINE;(R)-3-N-BOC-AMINO-PIPERIDINE;(R)-3-BOC-AMINOPIPERIDINE;(R)-(+)-3-TERT-BUTOXYCARBONYLAMINOPIPERIDINE;(R)-3-(TERT-BUTOXYCARBONYLAMINO)PIPERIDINE
• CAS NO: 309956-78-3
• Molecular Formula: C₁₀H₂₀N₂O₂
• Molecular Weight: 200.28
• EINECS: 1308068-626-2
• Product Categories: N-BOC;pharmacetical;Piperidine;Piperidine Series;Piperidines;Intermediates;(R)-3-(Boc-Amino)piperidine ada@tuskwei,com whatsapp;8618031153937
• Mol File: 309956-78-3.mol
• Article Data: 10

Chemical Properties

• Melting Point: 121.0 to 125.0 °C
• Boiling Point: 304.8 °C at 760 mmHg
• Flash Point: 138.2 °C
• Appearance: /
• Density: 1.02 g/cm³
• Vapor Pressure: 0.000854mmHg at 25°C
• Refractive Index: 1.479
• Storage Temp.: Room temperature.
• Solubility: Soluble in methanol and ethanol.
• PKA: 12.37±0.20(Predicted)
• BRN: 10662518
• CAS DataBase Reference: (R)-3-(Boc-Amino)piperidine(CAS DataBase Reference)
• NIST Chemistry Reference: (R)-3-(Boc-Amino)piperidine(309956-78-3)
• EPA Substance Registry System: (R)-3-(Boc-Amino)piperidine(309956-78-3)

Safety Data

• Hazard Codes: Xi,N
• Statements: 37/38-41-50
• Safety Statements: 26-39-61-29-36
• RIDADR: 3077
• WGK Germany: 2
• HazardClass: 9
• PackingGroup: Ⅲ
• Hazardous Substances Data: 309956-78-3(Hazardous Substances Data)

Usage

Solubility in organics

Soluble in methanol and ethanol.

Uses

Different sources of media describe the Uses of 309956-78-3 differently. You can refer to the following data:
1. (R)-3-(Boc-amino)piperidine is used as an organic chemical synthesis intermediate.
2. (R)-3-(Boc-amino)piperidine is Boc protected (R)-3-Aminopiperidine (A627920, Dihydrochloride salt) which has been used as a reactant for the preparation of dipeptidyl peptidase IV inhibitors derived from Alogliptin.

storage

Stable under recommended storage conditions. Incompatible with oxidizing agents.

Chemical Properties

White powder

InChI:InChI=1/C10H20N2O2/c1-10(2,3)14-9(13)12-8-5-4-6-11-7-8/h8,11H,4-7H2,1-3H3,(H,12,13)/t8-/m1/s1

Synthetic route

tert-butyl (R)-(+)-(N-benzylpiperidin-3-yl)carbamate (454713-13-4) → (R)-piperidin-3-ylcarbamic acid tert-butyl ester (309956-78-3)

Conditions	Yield
With 5%-palladium/activated carbon; hydrogen In ethanol at 20 - 25℃; under 150015 Torr; for 20h;	97%
With palladium 10% on activated carbon; hydrogen In methanol at 45℃; under 1140.08 Torr; for 2h;	85%
With hydrogen; 10% palladium on activated carbon In metahnol at 20℃; for 24h;

(R)-3-(tert-butoxycarbonylamino)piperidine-1-carboxylic acid benzyl ester (485820-12-0) → (R)-piperidin-3-ylcarbamic acid tert-butyl ester (309956-78-3)

Conditions	Yield
With palladium 10% on activated carbon; hydrogen In methanol; water at 35 - 40℃; under 2250.23 - 3000.3 Torr; for 2h; Time; Autoclave; Inert atmosphere;	95.4%
With hydrogen; palladium 10% on activated carbon In ethanol at 20℃; under 760.051 Torr; for 168h;	92%
In ethanol

t-butyl (R)-piperidin-3-ylcarbamate R-mandelate (1189160-63-1) → (R)-piperidin-3-ylcarbamic acid tert-butyl ester (309956-78-3)

Conditions	Yield
With sodium chloride; sodium hydroxide In water; butan-1-ol at 10 - 30℃;	79.7%

(R)-2-tert-butyloxycarbonylamino-1,5-pentanedimethanesulfonate → (R)-piperidin-3-ylcarbamic acid tert-butyl ester (309956-78-3)

Conditions	Yield
With ammonium hydroxide In acetonitrile at 30℃; for 48h;	74%
Multi-step reaction with 2 steps 1: 2 h / 45 °C 2: hydrogen; palladium 10% on activated carbon / methanol / 2 h / 45 °C / 1140.08 Torr View Scheme

D-Glutamic acid (6893-26-1) → (R)-piperidin-3-ylcarbamic acid tert-butyl ester (309956-78-3)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: thionyl chloride / 6 h / 30 °C 2.1: sodium tetrahydroborate; ethanol / 2 h / Cooling with ice; Reflux 3.1: triethylamine / dichloromethane / 0.5 h / 0 °C 3.2: 30 °C 4.1: ammonium hydroxide / acetonitrile / 48 h / 30 °C View Scheme
Multi-step reaction with 5 steps 1: water; N,N-dimethyl-formamide / 1 h / 20 - 30 °C 2: dimethylsulfide borane complex / tetrahydrofuran / 10 h / -5 - 50 °C 3: triethylamine / dichloromethane / 1 h / 0 - 20 °C 4: 2 h / 45 °C 5: hydrogen; palladium 10% on activated carbon / methanol / 2 h / 45 °C / 1140.08 Torr View Scheme

1,5-dimethyl (2R)-2-[[(tert-butoxy)carbonyl]amino]pentanedioate → (R)-piperidin-3-ylcarbamic acid tert-butyl ester (309956-78-3)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: sodium tetrahydroborate; ethanol / 2 h / Cooling with ice; Reflux 2.1: triethylamine / dichloromethane / 0.5 h / 0 °C 2.2: 30 °C 3.1: ammonium hydroxide / acetonitrile / 48 h / 30 °C View Scheme

di-tert-butyl dicarbonate (24424-99-5) → (R)-piperidin-3-ylcarbamic acid tert-butyl ester (309956-78-3)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: thionyl chloride / 6 h / 30 °C 2.1: sodium tetrahydroborate; ethanol / 2 h / Cooling with ice; Reflux 3.1: triethylamine / dichloromethane / 0.5 h / 0 °C 3.2: 30 °C 4.1: ammonium hydroxide / acetonitrile / 48 h / 30 °C View Scheme
Multi-step reaction with 5 steps 1: water; N,N-dimethyl-formamide / 1 h / 20 - 30 °C 2: dimethylsulfide borane complex / tetrahydrofuran / 10 h / -5 - 50 °C 3: triethylamine / dichloromethane / 1 h / 0 - 20 °C 4: 2 h / 45 °C 5: hydrogen; palladium 10% on activated carbon / methanol / 2 h / 45 °C / 1140.08 Torr View Scheme

tert-butyl N-[(2R)-1,5-dihydroxypentan-2-yl]carbamate → (R)-piperidin-3-ylcarbamic acid tert-butyl ester (309956-78-3)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: triethylamine / dichloromethane / 0.5 h / 0 °C 1.2: 30 °C 2.1: ammonium hydroxide / acetonitrile / 48 h / 30 °C View Scheme
Multi-step reaction with 3 steps 1: triethylamine / dichloromethane / 1 h / 0 - 20 °C 2: 2 h / 45 °C 3: hydrogen; palladium 10% on activated carbon / methanol / 2 h / 45 °C / 1140.08 Torr View Scheme

N-[(1,1-dimethylethoxy)carbonyl]-D-glutamic acid (34404-28-9) → (R)-piperidin-3-ylcarbamic acid tert-butyl ester (309956-78-3)

Conditions	Yield
Multi-step reaction with 4 steps 1: dimethylsulfide borane complex / tetrahydrofuran / 10 h / -5 - 50 °C 2: triethylamine / dichloromethane / 1 h / 0 - 20 °C 3: 2 h / 45 °C 4: hydrogen; palladium 10% on activated carbon / methanol / 2 h / 45 °C / 1140.08 Torr View Scheme

1-benzyloxycarbonylpiperidine-3-carboxylic acid (78190-11-1) → (R)-piperidin-3-ylcarbamic acid tert-butyl ester (309956-78-3)

Conditions

Yield

Multi-step reaction with 6 steps 1: methanol / 40 - 50 °C 2: ethanol / 70 - 75 °C 3: methanesulfonyl chloride; ammonia; N-ethyl-N,N-diisopropylamine / tetrahydrofuran / -10 - 25 °C 4: sodium hydroxide; sodium hypochlorite / water / 25 - 40 °C 5: sodium carbonate / methanol; water / 20 - 25 °C 6: palladium 10% on activated carbon; hydrogen / methanol; water / 2 h / 35 - 40 °C / 2250.23 - 3000.3 Torr / Autoclave; Inert atmosphere View Scheme

(R)-1-((benzyloxy)carbonyl)piperidine-3-carboxylic acid (160706-62-7) → (R)-piperidin-3-ylcarbamic acid tert-butyl ester (309956-78-3)

Conditions	Yield
Multi-step reaction with 4 steps 1: methanesulfonyl chloride; ammonia; N-ethyl-N,N-diisopropylamine / tetrahydrofuran / -10 - 25 °C 2: sodium hydroxide; sodium hypochlorite / water / 25 - 40 °C 3: sodium carbonate / methanol; water / 20 - 25 °C 4: palladium 10% on activated carbon; hydrogen / methanol; water / 2 h / 35 - 40 °C / 2250.23 - 3000.3 Torr / Autoclave; Inert atmosphere View Scheme

C14H18N2O3 → (R)-piperidin-3-ylcarbamic acid tert-butyl ester (309956-78-3)

Conditions	Yield
Multi-step reaction with 3 steps 1: sodium hydroxide; sodium hypochlorite / water / 25 - 40 °C 2: sodium carbonate / methanol; water / 20 - 25 °C 3: palladium 10% on activated carbon; hydrogen / methanol; water / 2 h / 35 - 40 °C / 2250.23 - 3000.3 Torr / Autoclave; Inert atmosphere View Scheme

C8H11N*C14H17NO4 → (R)-piperidin-3-ylcarbamic acid tert-butyl ester (309956-78-3)

Conditions

Yield

Multi-step reaction with 5 steps 1: ethanol / 70 - 75 °C 2: methanesulfonyl chloride; ammonia; N-ethyl-N,N-diisopropylamine / tetrahydrofuran / -10 - 25 °C 3: sodium hydroxide; sodium hypochlorite / water / 25 - 40 °C 4: sodium carbonate / methanol; water / 20 - 25 °C 5: palladium 10% on activated carbon; hydrogen / methanol; water / 2 h / 35 - 40 °C / 2250.23 - 3000.3 Torr / Autoclave; Inert atmosphere View Scheme

(R)-1-benzylpiperidine-3-carboxylic azide → (R)-piperidin-3-ylcarbamic acid tert-butyl ester (309956-78-3)

Conditions	Yield
Multi-step reaction with 3 steps 1: sulfuric acid / water / 1 h / 100 °C 2: sodium hydroxide / water / 2 h / 20 °C 3: 5%-palladium/activated carbon; hydrogen / ethanol / 20 h / 20 - 25 °C / 150015 Torr View Scheme

Ethyl nipecotate (71962-74-8) → (R)-piperidin-3-ylcarbamic acid tert-butyl ester (309956-78-3)

Conditions

Yield

Multi-step reaction with 7 steps 1: isopropyl alcohol; water / 0.5 h / Reflux 2: sodium carbonate / N,N-dimethyl-formamide / 12 h / 60 °C 3: hydrazine hydrate / butan-1-ol / 8 h / Reflux 4: sulfuric acid; sodium nitrite / water / 1 h / 0 - 5 °C 5: sulfuric acid / water / 1 h / 100 °C 6: sodium hydroxide / water / 2 h / 20 °C 7: 5%-palladium/activated carbon; hydrogen / ethanol / 20 h / 20 - 25 °C / 150015 Torr View Scheme

(R)-piperidine-3-carboxylic acid ethyl ester*l-tartaric acid → (R)-piperidin-3-ylcarbamic acid tert-butyl ester (309956-78-3)

Conditions	Yield
Multi-step reaction with 6 steps 1: sodium carbonate / N,N-dimethyl-formamide / 12 h / 60 °C 2: hydrazine hydrate / butan-1-ol / 8 h / Reflux 3: sulfuric acid; sodium nitrite / water / 1 h / 0 - 5 °C 4: sulfuric acid / water / 1 h / 100 °C 5: sodium hydroxide / water / 2 h / 20 °C 6: 5%-palladium/activated carbon; hydrogen / ethanol / 20 h / 20 - 25 °C / 150015 Torr View Scheme

(R)-1-benzylpiperidine-3-carboxylic acid ethyl ester (245529-50-4) → (R)-piperidin-3-ylcarbamic acid tert-butyl ester (309956-78-3)

Conditions	Yield
Multi-step reaction with 5 steps 1: hydrazine hydrate / butan-1-ol / 8 h / Reflux 2: sulfuric acid; sodium nitrite / water / 1 h / 0 - 5 °C 3: sulfuric acid / water / 1 h / 100 °C 4: sodium hydroxide / water / 2 h / 20 °C 5: 5%-palladium/activated carbon; hydrogen / ethanol / 20 h / 20 - 25 °C / 150015 Torr View Scheme

(R)-1- benzylpiperidine-3-carboxylic acid hydrazide → (R)-piperidin-3-ylcarbamic acid tert-butyl ester (309956-78-3)

Conditions	Yield
Multi-step reaction with 4 steps 1: sulfuric acid; sodium nitrite / water / 1 h / 0 - 5 °C 2: sulfuric acid / water / 1 h / 100 °C 3: sodium hydroxide / water / 2 h / 20 °C 4: 5%-palladium/activated carbon; hydrogen / ethanol / 20 h / 20 - 25 °C / 150015 Torr View Scheme

(3R)-1-benzyl-3-aminopiperidine (168466-84-0) → (R)-piperidin-3-ylcarbamic acid tert-butyl ester (309956-78-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: sodium hydroxide / water / 2 h / 20 °C 2: 5%-palladium/activated carbon; hydrogen / ethanol / 20 h / 20 - 25 °C / 150015 Torr View Scheme

(R)-piperidin-3-ylcarbamic acid tert-butyl ester (309956-78-3) + 4-(methylamino)-3-nitrobenzoic acid (41263-74-5) → 1,1-dimethylethyl ((3R)-1-{[4-(methylamino)-3-nitrophenyl]carbonyl}-3-piperidinyl)carbamate (1549812-10-3)

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 16h;	100%
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 16h;	100%
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 16h;	100%

(R)-piperidin-3-ylcarbamic acid tert-butyl ester (309956-78-3) + 3-methoxy-4-(methylamino)-5-nitrobenzoic acid (1549812-23-8) → (R)-(1-(3-methoxy-4-(methylamino)-5-nitrobenzoyl)piperidin-3-yl)carbamic acid tert-butyl ester (1549812-25-0)

Conditions	Yield
Stage #1: 3-methoxy-4-(methylamino)-5-nitrobenzoic acid 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 tetrahydrofuran; N,N-dimethyl-formamide for 0.666667h; Cooling with ice; Stage #2: (R)-piperidin-3-ylcarbamic acid tert-butyl ester In tetrahydrofuran; N,N-dimethyl-formamide at 20℃; for 10h; Solvent; Temperature;	100%
Stage #1: 3-methoxy-4-(methylamino)-5-nitrobenzoic acid 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 for 0.5h; Stage #2: (R)-piperidin-3-ylcarbamic acid tert-butyl ester In N,N-dimethyl-formamide for 1.5h;	19.4 g
Stage #1: 3-methoxy-4-(methylamino)-5-nitrobenzoic acid 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 for 0.5h; Stage #2: (R)-piperidin-3-ylcarbamic acid tert-butyl ester In N,N-dimethyl-formamide for 1.5h;	19.4 g
Stage #1: 3-methoxy-4-(methylamino)-5-nitrobenzoic acid 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 for 0.5h; Stage #2: (R)-piperidin-3-ylcarbamic acid tert-butyl ester In N,N-dimethyl-formamide for 1.5h;	19.4 g

(R)-piperidin-3-ylcarbamic acid tert-butyl ester (309956-78-3) + 3-bromo-5-fluoropyridine-2- carbonitrile (950670-18-5) → (R)-tert-butyl 1-(5-bromo-6-cyanopyridin-3-yl)piperidin-3-ylcarbamate

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In 1-methyl-pyrrolidin-2-one at 100℃; for 1.5h;	100%

(R)-piperidin-3-ylcarbamic acid tert-butyl ester (309956-78-3) + methyl 4-(6-carbamoyl-3-(methylthio)-1,2,4-triazin-5-ylamino)benzoate → (R)-methyl 4-(3-(3-(tert-butoxycarbonylamino)piperidin-1-yl)-6-carbamoyl-1,2,4-triazin-5-ylamino)benzoate

Conditions	Yield
Stage #1: methyl 4-(6-carbamoyl-3-(methylthio)-1,2,4-triazin-5-ylamino)benzoate With 3-chloro-benzenecarboperoxoic acid In 1-methyl-pyrrolidin-2-one at 20℃; for 1h; Stage #2: (R)-piperidin-3-ylcarbamic acid tert-butyl ester With N-ethyl-N,N-diisopropylamine In 1-methyl-pyrrolidin-2-one at 90℃; for 1.5h;	100%

(R)-piperidin-3-ylcarbamic acid tert-butyl ester (309956-78-3) + 5-chloro-2-(4-cyano-3-fluorophenyl)-1-(3-fluoro-4-methoxyphenyl)imidazole-4-carboxylic acid → tert-butyl N-[(3R)-1-[5-Chloro-2-(4-cyano-3-fluorophenyl)-1-(3-fluoro-4-methoxyphenyl)imidazole-4-carbonyl]piperidin-3-yl]carbamate

Conditions	Yield
With 4-methyl-morpholine; 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 1h;	100%

(R)-piperidin-3-ylcarbamic acid tert-butyl ester (309956-78-3) + 2-(4-Cyano-3-fluorophenyl)-1-(3-fluoro-4-methoxyphenyl)imidazole-4-carboxylic acid → tert-butyl N-[(3R)-1-[2-(4-cyano-3-fluorophenyl)-1-(3-fluoro-4-1methoxyphenyl)imidazole-4-carbonyl]piperidin-3-yl]carbamate

Conditions	Yield
With 4-methyl-morpholine; 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 1h;	100%

(R)-piperidin-3-ylcarbamic acid tert-butyl ester (309956-78-3) + 4-chloro-1H-pyrrolo[2,3-d]pyrimidine (3680-69-1) → (R)-tert-butyl (1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-3-yl)carbamate

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In butan-1-ol at 80℃; for 52h; Inert atmosphere; Sealed tube;	100%

(R)-piperidin-3-ylcarbamic acid tert-butyl ester (309956-78-3) + 2-chloro-6,7-dimethoxyquinazolin-4-amine (23680-84-4) → tert-butyl (R)-(1-(4-amino-6,7-dimethoxyquinazolin-2-yl)piperidin-3-yl)carbamate

Conditions	Yield
In i-Amyl alcohol at 130℃; under 760.051 Torr; for 0.833333h; Microwave irradiation;	100%

(R)-piperidin-3-ylcarbamic acid tert-butyl ester (309956-78-3) + 1-(but-2-ynyl)-6-chloro-3-(prop-2-ynyl)pyrimidine-2,4(1H,3H)-dione → tert-butyl (R)-(1-(3-(but-2-yn-1-yl)-2,6-dioxo-1-(prop-2-yn-1-yl)-1,2,3,6-tetrahydropyrimidin-4-yl)piperidin-3-yl)carbamate

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 65℃; for 5h;	99.8%
With potassium carbonate In N,N-dimethyl-formamide at 65℃; for 5h;	99%

(R)-piperidin-3-ylcarbamic acid tert-butyl ester (309956-78-3) → 3-(R)-aminopiperidine dihydrochloride

Conditions	Yield
With hydrogenchloride In tert-butyl methyl ether at 0 - 20℃; for 8h;	99%
With thionyl chloride In methanol at 30℃; for 10h;

(R)-piperidin-3-ylcarbamic acid tert-butyl ester (309956-78-3) + C13H12ClN3O2 → C23H31N5O4

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 65℃; Temperature;	98.2%

(R)-piperidin-3-ylcarbamic acid tert-butyl ester (309956-78-3) + (1aS,6aR)-3,5-dichloro-6,6a-di-hydro-1aH-1-oxa-cyclopropa[a]indene (1215279-81-4) → tert-butyl (R)-1-((1R,2R)-4,6-dichloro-2-hydroxy-2,3-dihydro-1H-inden-1-yl)piperidin-3-ylcarbamate (1571103-69-9)

Conditions	Yield
In acetonitrile at 80℃; regioselective reaction;	98%
In acetonitrile at 70℃; for 15h;	330 mg

(R)-piperidin-3-ylcarbamic acid tert-butyl ester (309956-78-3) + 7-but-2-ynyl-8-iodo-3-methyl-1-(4-methyl-quinazolin-2-ylmethyl)-3,7-dihydro-purine-2,6-dione → 1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[(R)-3-(tert-butoxycarbonylamino)-piperidin-1-yl]-2,6-dioxo-2,3,6,7-tetrahydro-1H-purine

Conditions	Yield
With lithium hexamethyldisilazane In toluene at 60 - 65℃; Reagent/catalyst; Inert atmosphere;	97.8%
With lithium hexamethyldisilazane In toluene at 60 - 65℃; Reagent/catalyst; Inert atmosphere;	97.8%

(R)-piperidin-3-ylcarbamic acid tert-butyl ester (309956-78-3) + 3,5-dichloro-pyrazine-2-carbonitrile (313339-92-3) → tert-butyl N-[(3R)-1-(6-chloro-5-cyanopyrazin-2-yl)piperidin-3-yl]carbamate

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; for 1.5h;	97%
With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; for 1.5h;	93%
With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; for 1.5h;	2.5 g

(R)-piperidin-3-ylcarbamic acid tert-butyl ester (309956-78-3) + 2,3-dichloro-5-trifluoromethylpyridine (69045-84-7) → (R)-tert-butyl (1-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)piperidin-3-yl)carbamate

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 100℃; for 5h;	97%

(R)-piperidin-3-ylcarbamic acid tert-butyl ester (309956-78-3) + C18H13BrFN5O3 → C28H32FN7O5

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 75℃; for 2h;	96.1%

(R)-piperidin-3-ylcarbamic acid tert-butyl ester (309956-78-3) + benzyl chloroformate (501-53-1) → (R)-3-(tert-butoxycarbonylamino)piperidine-1-carboxylic acid benzyl ester (485820-12-0)

Conditions	Yield
With triethylamine In tetrahydrofuran at 0 - 5℃; for 24h;	96%
With sodium hydrogencarbonate In tetrahydrofuran; water at 20℃; for 4h; Saturated solution;
With triethylamine In tetrahydrofuran at 0 - 5℃; for 24h;

(R)-piperidin-3-ylcarbamic acid tert-butyl ester (309956-78-3) + 2-((6-chloro-3-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)methyl)benzonitrile (865758-96-9) → 2-[[6-[(3R)-3-tert-butoxycarbonylamino-1-piperidinyl]-3,4-dihydro-2,4-dioxo-3-methyl-1(2H)-pyrimidinyl]methyl]benzonitrile (1246610-74-1)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 75℃; for 6h; Product distribution / selectivity;	96%
With potassium carbonate at 80 - 90℃;	90%
With tetrabutylammomium bromide; potassium carbonate; sodium iodide In acetonitrile for 25h; Reflux;	89.3%

(R)-piperidin-3-ylcarbamic acid tert-butyl ester (309956-78-3) + 6-amino-1-(2-cyanobenzyl)-3-methylpyrimidine-2,4(1H,3H)-dione (1246610-77-4) + (R)-piperidin-3-ylcarbamic acid tert-butyl ester hydrochloride (1217656-59-1) → 2-[[6-[(3R)-3-tert-butoxycarbonylamino-1-piperidinyl]-3,4-dihydro-2,4-dioxo-3-methyl-1(2H)-pyrimidinyl]methyl]benzonitrile (1246610-74-1)

Conditions	Yield
at 100℃; for 3h;	96%

(R)-piperidin-3-ylcarbamic acid tert-butyl ester (309956-78-3) + Bromodiphenylmethane (776-74-9) → (R)-tert-butyl (1-benzhydrylpiperidin-3-yl)carbamate

Conditions	Yield
With triethylamine In dichloromethane at 60℃; for 14h;	96%

(R)-piperidin-3-ylcarbamic acid tert-butyl ester (309956-78-3) + 2-bromo-1-(but-2-ynyl)-4-methyl-6-((4-methylquinazolin-2-yl)methyl)-1H-imidazo[4,5-b]pyridine-5,7-(4H,6H)-dione (853029-57-9) → 1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[(R)-3-(tert-butoxycarbonylamino)-piperidin-1-yl]-2,6-dioxo-2,3,6,7-tetrahydro-1H-purine

Conditions	Yield
With potassium carbonate In dimethyl sulfoxide; acetonitrile at 84 - 86℃; for 20h;	95.3%
With potassium carbonate In dimethyl sulfoxide; acetonitrile at 20 - 86℃; for 20h; Temperature;	95.3%
With potassium carbonate; potassium iodide In dimethyl sulfoxide at 80 - 85℃; Reagent/catalyst;	91%

(R)-piperidin-3-ylcarbamic acid tert-butyl ester (309956-78-3) + 8-bromo-7-(but-2-yn-1-yl)-3-methyl-2,,6-dihydro-1H-purine-2,6-dione (666816-98-4) + 2-chloromethyl-4-methylquinazoline (109113-72-6) → 1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[(R)-3-(tert-butoxycarbonylamino)-piperidin-1-yl]-2,6-dioxo-2,3,6,7-tetrahydro-1H-purine

Conditions	Yield
Stage #1: 8-bromo-7-(but-2-yn-1-yl)-3-methyl-3,7-dihydro-1H-purine-2,6-dione; 2-chloromethyl-4-methylquinazoline With potassium carbonate In 1-methyl-pyrrolidin-2-one; acetonitrile at 50℃; for 6h; Stage #2: (R)-piperidin-3-ylcarbamic acid tert-butyl ester In 1-methyl-pyrrolidin-2-one; acetonitrile at 60℃; for 8h; Solvent; Temperature;	95.1%
With sodium carbonate at 55 - 60℃; for 6h; Concentration; Reagent/catalyst;	91.8%
Stage #1: (R)-piperidin-3-ylcarbamic acid tert-butyl ester; 8-bromo-7-(but-2-yn-1-yl)-3-methyl-3,7-dihydro-1H-purine-2,6-dione With 1-methyl-pyrrolidin-2-one; potassium carbonate; potassium iodide for 10h; Stage #2: 2-chloromethyl-4-methylquinazoline for 12h; Time;	90%
Stage #1: 8-bromo-7-(but-2-yn-1-yl)-3-methyl-3,7-dihydro-1H-purine-2,6-dione; 2-chloromethyl-4-methylquinazoline With potassium carbonate; potassium iodide In 1-methyl-pyrrolidin-2-one at 40 - 50℃; Stage #2: (R)-piperidin-3-ylcarbamic acid tert-butyl ester Reagent/catalyst; Solvent; Temperature;	86.7%
Stage #1: 8-bromo-7-(but-2-yn-1-yl)-3-methyl-3,7-dihydro-1H-purine-2,6-dione; 2-chloromethyl-4-methylquinazoline With potassium carbonate; potassium iodide In 1-methyl-pyrrolidin-2-one at 40 - 50℃; Stage #2: (R)-piperidin-3-ylcarbamic acid tert-butyl ester In 1-methyl-pyrrolidin-2-one Reagent/catalyst; Solvent; Temperature;

(R)-piperidin-3-ylcarbamic acid tert-butyl ester (309956-78-3) + N-ethoxycarbonyl-4-piperidone (29976-53-2) → C18H33N3O4 (1346006-05-0)

Conditions	Yield
With sodium tris(acetoxy)borohydride In 1,2-dichloro-ethane	95%

(R)-piperidin-3-ylcarbamic acid tert-butyl ester (309956-78-3) + 7-but-2-ynyl-8-iodo-3-methyl-1-(4-methyl-quinazolin-2-ylmethyl)-3,7-dihydro-purine-2,6-dione → Linagliptin

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 80℃; for 10h;	94.1%

(R)-piperidin-3-ylcarbamic acid tert-butyl ester (309956-78-3) + 1-fluoro-2-nitro-4-trifluoromethyl-benzene (367-86-2) → (R)-tert-butyl 1-(2-nitro-4-(trifluoromethyl)phenyl)piperidin-3-ylcarbamate

Conditions	Yield
With sodium hydrogencarbonate In tetrahydrofuran at 70℃; for 14h;	94%

(R)-piperidin-3-ylcarbamic acid tert-butyl ester (309956-78-3) + 8-bromo-7-(but-2-yn-1-yl)-3-methyl-2,,6-dihydro-1H-purine-2,6-dione (666816-98-4) → 3-methyl-7-(2-butyn-1-yl)-8-[(R)-3-(tert-butoxycarbonylamino)piperidin-1-yl]xanthine (666816-91-7)

Conditions	Yield
With potassium carbonate In dimethyl sulfoxide at 114℃; for 6h;	94%
With potassium carbonate In dimethyl sulfoxide at 114℃; for 6h;	94%
With potassium carbonate In dimethyl sulfoxide at 114℃; for 6h;	94%

(R)-piperidin-3-ylcarbamic acid tert-butyl ester (309956-78-3) + 1-[4-chloro-6-(4-morpholinyl)-1,3,5-triazin-2-yl]-2-(difluoromethyl)-4-methoxy-1H-benzimidazole (1188914-98-8) → tert-butyl (R)-1-[4-[2-(difluoromethyl)-4-methoxy-1H-benzimidazol-1-yl]-6-(4-morpholinyl)-1,3,5-triazin-2-yl]piperidin-3-ylcarbamate (1188915-59-4)

Conditions	Yield
	94%
With N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 20℃;	94%

(R)-piperidin-3-ylcarbamic acid tert-butyl ester (309956-78-3) + 1-[4-chloro-6-(4-morpholinyl)-1,3,5-triazin-2-yl]-2-(difluoromethyl)-4-methoxy-1H-benzimidazole (1188914-98-8) → tert-butyl (S)-1-[4-[2-(difluoromethyl)-4-methoxy-1H-benzimidazol-1-yl]-6-(4-morpholinyl)-1,3,5-triazin-2-yl]piperidin-3-ylcarbamate (1188915-61-8)

Conditions	Yield
at 20℃;	94%

Upstream product

• 454713-13-4 tert-butyl (R)-(+)-(N-benzylpiperidin-3-yl)carbamate 
• 34404-28-9 N-[(1,1-dimethylethoxy)carbonyl]-D-glutamic acid 
• 71962-74-8 Ethyl nipecotate 
• 163343-71-3 (R)-piperidine-3-carboxylic acid ethyl ester*l-tartaric acid 
• 245529-50-4 (R)-1-benzylpiperidine-3-carboxylic acid ethyl ester 
• 168466-84-0 (3R)-1-benzyl-3-aminopiperidine 
• 16682-12-5 D-ornithine hydrochloride 
• 221874-51-7 (3R)-3-[(tert -butoxycarbonyl)amino]-2-piperidone 
• 88763-76-2 (R)-(+)-3-Amino-2-piperidinon 
• 1050446-94-0 C₁₄H₁₈N₂O₃ 
• 160706-62-7 (R)-1-((benzyloxy)carbonyl)piperidine-3-carboxylic acid 
• 78190-11-1 1-benzyloxycarbonylpiperidine-3-carboxylic acid 
• 397246-12-7 tert-butyl N-[(2R)-1,5-dihydroxypentan-2-yl]carbamate 
• 24424-99-5 di-tert-butyl dicarbonate 

Downstream Products

• 868609-89-6 [(R)-1-(4-bromo-phenyl)-piperidin-3-yl]-carbamic acid-tert-butylester 
• 485820-12-0 (R)-3-(tert-butoxycarbonylamino)piperidine-1-carboxylic acid benzyl ester 
• 1196507-77-3 (R)-tert-butyl 1-(3-benzamido-5-bromo-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate 
• 1196507-83-1 (R)-tert-butyl 1-(5-bromo-3-(3-methylbenzamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate 
• 1196508-39-0 (R)-tert-butyl 1-(5-bromo-3-(3-methoxybenzamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate 
• 1196508-54-9 (R)-tert-butyl 1-(5-bromo-3-(3-fluorobenzamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate 
• 1196508-97-0 (R)-tert-butyl 1-(5-bromo-3-(3-chloro-4-fluorobenzamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate 
• 1196508-99-2 (R)-tert-butyl 1-(5-bromo-3-(3-fluoro-4-methoxybenzamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate 
• 1196509-03-1 (R)-tert-butyl 1-(5-bromo-3-(1-(4-methoxybenzyl)-1H-pyrazole-4-carboxamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate 
• 1258316-02-7 (R)-tert-butyl 1-(5-carbamoyl-6-(4-(morpholine-4-carbonyl)phenylamino)pyridin-2-yl)piperidin-3-ylcarbamate 
• 1258316-45-8 (R)-tert-butyl 1-(5-carbamoyl-4-(4-(morpholine-4-carbonyl)phenylamino)pyridin-2-yl)piperidin-3-ylcarbamate 
• 894794-68-4 C₂₁H₂₆ClN₅O₂ 
• 894794-69-5 N-(1-{(3R)-3-[(tert-Butoxycarbonyl)amino]-piperidin-1-yl}-2,2-dicyanovinyl)-N-(2-chlorobenzyl)glycine ethyl ester 
• 894794-67-3 ethyl 3-amino-5-{(3R)-3-[(tert-butoxycarbonyl)-amino]piperidin-1-yl}-1-(2-chlorobenzyl)-4-cyano-1H-pyrrole-2-carboxylate 

Relevant articles and documents

Convenient synthesis of (R)-3-[(tert -Butoxycarbonyl)amino]piperidine and (R)-3-[(tert -Butoxycarbonyl)amino]azepane

(R)-3-[(tert -Butoxycarbonyl)amino]piperidine and (R)-3-[(tert -butoxycarbonyl)amino]azepane were prepared in two steps starting from d -ornithine and d -lysine, respectively. In the key step, N -Boc-protected 3-aminolactams were converted into imido esters by O-alkylation and then hydrogenated to amines, under mild conditions (5 bar H 2, room temperature) and without isolation, over a standard hydrogenation catalyst (5% Pt/C).

(R)- 3 - Boc - amino piperidine preparation method

The invention discloses a preparation method of (R)-3-Boc-aminopiperidine and relates to the technical field of preparation of piperidine heterocyclic compounds. The preparation method includes following steps: (1) with N-Cbz-3-piperidinecarboxylic acid as a raw material, performing chiral resolution with R-phenylethylamine to obtain a compound I; (2) performing an acid-amide condensation reaction to the compound I and ammonia gas to obtain a compound II; (3) performing a Hofmann degradation reaction to the compound II to obtain a compound III; (4) performing protection to the compound III with di-tert-butyl dicarbonate to obtain a compound IV; and (5) performing a hydrogenation and Cbz-removal reaction to the compound IV to prepare the (R)-3-Boc-aminopiperidine. The method is mild in reaction conditions, is safe and reliable, is excellent in process stability, is low in energy consumption, is high in yield, is green and environment-protective and is suitable for industrial production.

(R) - 3-amino-piperidine dihydrochloride preparation method

The invention discloses a method for preparing (R)-3-amino piperidine hydrochloride. D-glutamic acid is taken as a starting material, and the (R)-3-amino piperidine hydrochloride is obtained by reaction in the following five steps: (1) hydroxyl esterification and amido Boc protection; (2) ester reduction; (3) hydroxyl activation; (4) cyclization; (5) amino Boc removal protection. The preparation method disclosed by the invention is short in synthetic route and low in cost, and industrial production can be achieved.