216854-23-8

Basic information

• Product Name: (S)-3-N-Boc-aminopiperidine
• Synonyms: (S)-TERT-BUTYL-PIPERIDIN-3-YLCARBAMATE;(S)-PIPERIDIN-3-YL-CARBAMIC ACID TERT-BUTYL ESTER;(S)-(-)-3-TERT-BUTOXYCARBONYLAMINOPIPERIDINE;(S)-3-(TERT-BUTOXYCARBONYLAMINO)PIPERIDINE;(S)-3-N-BOC-AMINOPIPERIDINE;(S)-3-BOC-AMINOPIPERIDINE;CARBAMIC ACID, (3S)-3-PIPERIDINYL-, 1,1-DIMETHYLETHYL ESTER;Carbamic acid, (3S)-3-piperidinyl-, 1,1-dimethylethyl ester (9CI)
• CAS NO: 216854-23-8
• Molecular Formula: C₁₀H₂₀N₂O₂
• Molecular Weight: 200.28
• EINECS: 1592732-453-0
• Product Categories: N-BOC;pharmacetical;Piperidine;Piperidine Series;Piperidines;Chiral Building Blocks;Heterocyclic Building Blocks;Amines;Heterocycles;Heterocycle-other series
• Mol File: 216854-23-8.mol
• Article Data: 3

Chemical Properties

• Melting Point: 122-127°C
• Boiling Point: 304.8 °C at 760 mmHg
• Flash Point: 138.2 °C
• Appearance: White to off-white/Crystalline Powder
• Density: 1.02 g/cm³
• Vapor Pressure: 0.000854mmHg at 25°C
• Refractive Index: 1.479
• Storage Temp.: Room temperature.
• Solubility: Freely soluble in ethanol.
• PKA: 12.37±0.20(Predicted)
• CAS DataBase Reference: (S)-3-N-Boc-aminopiperidine(CAS DataBase Reference)
• NIST Chemistry Reference: (S)-3-N-Boc-aminopiperidine(216854-23-8)
• EPA Substance Registry System: (S)-3-N-Boc-aminopiperidine(216854-23-8)

Safety Data

• Hazard Codes: Xi
• Statements: 37/38-41-36/37/38
• Safety Statements: 26-39-37/39
• WGK Germany: 3
• Hazardous Substances Data: 216854-23-8(Hazardous Substances Data)

Usage

Chemical Properties

White powder

Uses

Different sources of media describe the Uses of 216854-23-8 differently. You can refer to the following data:
1. (S)-3-N-Boc-aminopiperidine can be useful intermediate for the synthesis of a variety of chiral aminopiperidinyl quinolones as potent antibacterial agents against resistant pathogens; and alkynylpyrimidine amide derivatives as orally a vailable inhibitors of Tie-2 kinase.
2. (S)-3-(Boc-amino)piperidine, is used as an intermediate for pigments. It is also used as important raw material and intermediate used in organic Synthesis, pharmaceuticals, agrochemicals and dyestuff. It is also an useful intermediate for the synthesis of a variety of chiral aminopiperidinyl quinolones as potent antibacterial agents against resistant pathogens; and alkynylpyrimidine amide derivatives as orally available inhibitors of Tie-2 kinase.

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-/m0/s1

Synthetic route

3(S)-<(butoxycarbonyl)amino>-2-oxopiperidine (92235-39-7) → tert-butyl (S)-piperidin-3-yl-carbamate (216854-23-8)

Conditions	Yield
With borane-THF In tetrahydrofuran at 0 - 25℃; for 6.75h;	30%

(S)-2-(tert-butoxycarbonylamino)pentane-1,5-diyl dimethanesulfonate (607376-86-3) → tert-butyl (S)-piperidin-3-yl-carbamate (216854-23-8)

Conditions	Yield
With ammonium hydroxide In acetonitrile for 48h; Ambient temperature; Yield given;

L-glutamic acid (56-86-0) + 2-benzyloxycarbonylaminomethyl-4-benzyliden-Δ2-oxazolinone-(5) → tert-butyl (S)-piperidin-3-yl-carbamate (216854-23-8)

Conditions	Yield
Multi-step reaction with 5 steps 1: H2SO4 / 2 h / Heating 2: Et3N / dioxane; H2O / 2 h / 0 °C 3: NaBH4, CaCl2 / ethanol / 2 h / 0 °C 4: Et3N / CH2Cl2 / 1 h / -10 - 0 °C 5: aq. NH4OH / acetonitrile / 48 h / Ambient temperature View Scheme

L-glutamic acid dimethyl ester (6525-53-7, 16422-27-8, 40149-68-6) → tert-butyl (S)-piperidin-3-yl-carbamate (216854-23-8)

Conditions	Yield
Multi-step reaction with 4 steps 1: Et3N / dioxane; H2O / 2 h / 0 °C 2: NaBH4, CaCl2 / ethanol / 2 h / 0 °C 3: Et3N / CH2Cl2 / 1 h / -10 - 0 °C 4: aq. NH4OH / acetonitrile / 48 h / Ambient temperature View Scheme

dimethyl (2S)-2-[(tert-butoxycarbonyl)amino]pentanedioate (59279-60-6, 130622-05-8) → tert-butyl (S)-piperidin-3-yl-carbamate (216854-23-8)

Conditions	Yield
Multi-step reaction with 3 steps 1: NaBH4, CaCl2 / ethanol / 2 h / 0 °C 2: Et3N / CH2Cl2 / 1 h / -10 - 0 °C 3: aq. NH4OH / acetonitrile / 48 h / Ambient temperature View Scheme

[(1S)-4-hydroxy-1-(hydroxymethyl)butyl]carbamic acid tert-butyl ester (162955-48-8) → tert-butyl (S)-piperidin-3-yl-carbamate (216854-23-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: Et3N / CH2Cl2 / 1 h / -10 - 0 °C 2: aq. NH4OH / acetonitrile / 48 h / Ambient temperature View Scheme

1-[4-chloro-6-(4-morpholinyl)-1,3,5-triazin-2-yl]-2-(difluoromethyl)-4-methoxy-1H-benzimidazole (1188914-98-8) + tert-butyl (S)-piperidin-3-yl-carbamate (216854-23-8) → 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
at 20℃;	100%

1-[5-(difluoromethyl)-6-fluoro-2-pyridyl]-6-(6-methylpyrazin-2-yl)pyrazolo[4,3-c]pyridine (1527525-60-5) + tert-butyl (S)-piperidin-3-yl-carbamate (216854-23-8) → tert-butyl N-[(3S)-1-[3-(difluoromethyl)-6-[6-(6-methylpyrazin-2-yl)pyrazolo[4,3-c]pyridin-1-yl]-2-pyridyl]-3-piperidyl]carbamate (1527525-62-7)

Conditions	Yield
With 4-methyl-morpholine In 1-methyl-pyrrolidin-2-one at 100℃; Sealed tube;	100%

2-chloro-6,7-dimethoxyquinazolin-4-amine (23680-84-4) + tert-butyl (S)-piperidin-3-yl-carbamate (216854-23-8) → tert-butyl (S)-(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%

1-[4-chloro-6-(4-morpholinyl)-1,3,5-triazin-2-yl]-2-(difluoromethyl)-4-methoxy-1H-benzimidazole (1188914-98-8) + tert-butyl (S)-piperidin-3-yl-carbamate (216854-23-8) → 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
With N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 20℃;	100%

phenylacetaldehyde (122-78-1) + tert-butyl (S)-piperidin-3-yl-carbamate (216854-23-8) → (S)-tert-butyl 1-phenethylpiperidin-3-ylcarbamate (1361322-88-4)

Conditions	Yield
With sodium tris(acetoxy)borohydride; acetic acid In dichloromethane at 20℃; for 4.25h;	99%

benzyl chloroformate (501-53-1) + tert-butyl (S)-piperidin-3-yl-carbamate (216854-23-8) → benzyl (3S)-3-[(2-methylpropan-2-yl)oxycarbonylamino]piperidine-1-carboxylate (876379-22-5)

Conditions	Yield
With triethylamine In dichloromethane at 0 - 20℃;	99%
With triethylamine In dichloromethane at 0℃; for 1h;	95%
With triethylamine In ethyl acetate at 0℃; for 1h;	95%
With triethylamine In dichloromethane at 0 - 20℃; Product distribution / selectivity;	89%
With triethylamine In tetrahydrofuran at 20℃; for 0.5h;

Bromodiphenylmethane (776-74-9) + tert-butyl (S)-piperidin-3-yl-carbamate (216854-23-8) → (S)-tert-butyl (1-benzhydrylpiperidin-3-yl)carbamate

Conditions	Yield
With triethylamine In dichloromethane at 60℃; for 14h;	94%

2-methylpropane-1-sulfonyl chloride (35432-36-1) + tert-butyl (S)-piperidin-3-yl-carbamate (216854-23-8) → [(S)-1-(2-methyl-propane-1-sulfonyl)-piperidin-3-yl]-carbamic acid tert-butyl ester (1270496-69-9)

Conditions	Yield
With triethylamine In dichloromethane at 0 - 20℃;	93%

7-chloro-6-nitrothieno[3,2-b]pyridine (110651-92-8) + tert-butyl (S)-piperidin-3-yl-carbamate (216854-23-8) → tert-butyl [(3S)-1-(6-nitrothieno[3,2-b]pyridin-7-yl)piperidin-3-yl]carbamate (1620011-13-3)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In butan-1-ol at 110℃; for 12h;	93%

2-chloro-4-((2-isopropyl-6-(4-methoxyphenyl)pyridin-4-yl)amino)pyrimidine-5-carboxamide + tert-butyl (S)-piperidin-3-yl-carbamate (216854-23-8) → tert-butyl (S)-(1-(5-carbamoyl-4-((2-isopropyl-6-(4-methoxyphenyl)pyridin-4-yl)amino)pyrimidin-2-yl)piperidin-3-yl)carbamate

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In 1,4-dioxane at 90℃; for 1h;	92%

4-chloro-9-(2-trimethylsilanyl-ethoxymethyl)-9H-dipyrido[2,3-b;4',3'-d]pyrrole-6-carbonitrile (1200130-66-0) + tert-butyl (S)-piperidin-3-yl-carbamate (216854-23-8) → (S)-tert-butyl 1-(6-cyano-9-((2-(trimethylsilyl)ethoxy)methyl)-9H-dipyrido[2,3-b;4',3'-d]pyrrol-4-yl)piperidin-3-ylcarbamate (1312753-95-9)

Conditions	Yield
In N,N-dimethyl acetamide at 100℃; for 2h;	90%

di-tert-butyl (6-bromo-2-pyridinyl)imidodicarbonate (870703-61-0) + tert-butyl (S)-piperidin-3-yl-carbamate (216854-23-8) → (S)-tert-butyl 6-(3-aminopiperidin-1-yl)pyridin-2-ylcarbamate hydrochloride

Conditions	Yield
Stage #1: di-tert-butyl (6-bromo-2-pyridinyl)imidodicarbonate; tert-butyl (S)-piperidin-3-yl-carbamate With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene In N,N-dimethyl-formamide at 95℃; for 7h; Inert atmosphere; Stage #2: With hydrogenchloride In 1,4-dioxane at 20℃; for 7h;	90%

formaldehyd (50-00-0) + tert-butyl (S)-piperidin-3-yl-carbamate (216854-23-8) → (S)-tert-butyl (1-methylpiperidin-3-yl)carbamate (902152-77-6)

Conditions	Yield
With formic acid In 2-methyltetrahydrofuran; water at 80℃; for 0.75h;	90%

3-(6-fluoropyridin-2-yl)-1-methyl-5-(pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine + tert-butyl (S)-piperidin-3-yl-carbamate (216854-23-8) → (S)-tert-butyl 1-(6-(1-methyl-5-(pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)pyridin-2-yl)piperidin-3-ylcarbamate

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In ethanol at 100℃; for 15h;	90%

5-iodo-6-nitro-1,2,3,4-tetrahydro-1,8-naphthyridine (1620012-10-3) + tert-butyl (S)-piperidin-3-yl-carbamate (216854-23-8) → tert-butyl [(3S)-1-(3-nitro-5,6,7,8-tetrahydro-1,8-naphthyridin-4-yl)piperidin-3-yl]carbamate (1620012-11-4)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In butan-1-ol at 140℃; for 14h;	89%

5-(4-chlorophenyl)-2-furoic acid (41019-45-8) + tert-butyl (S)-piperidin-3-yl-carbamate (216854-23-8) → tert-butyl N-[(3S)-1-[5-(4-chlorophenyl)furan-2-carbonyl]piperidin-3-yl]carbamate

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 1h;	89%

2-chloro-4-((2,6-diisopropylpyridin-4-yl)amino)pyrimidine-5-carboxamide + tert-butyl (S)-piperidin-3-yl-carbamate (216854-23-8) → tert-butyl (S)-(1-(5-carbamoyl-4-((2,6-diisopropylpyridin-4-yl)amino)pyrimidin-2-yl)piperidine -3-yl)carbamate

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In 1,4-dioxane at 90℃; for 0.5h;	88%
With N-ethyl-N,N-diisopropylamine In 1,4-dioxane at 90℃; for 0.5h;	88%

4-(3-bromoimidazo[1,2-a]pyridin-6-yl)benzoic acid + tert-butyl (S)-piperidin-3-yl-carbamate (216854-23-8) → (S)-tert-butyl (1-(4-(3-bromoimidazo[1,2-a]pyridin-6-yl)benzoyl)piperidin-4-yl)carbamate

Conditions	Yield
With dmap; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In N,N-dimethyl-formamide at 40℃; for 8h;	88%

Upstream product

• 92235-39-7 3(S)-<(butoxycarbonyl)amino>-2-oxopiperidine 
• 162955-48-8 [(1S)-4-hydroxy-1-(hydroxymethyl)butyl]carbamic acid tert-butyl ester 
• 59279-60-6 dimethyl (2S)-2-[(tert-butoxycarbonyl)amino]pentanedioate 
• 6525-53-7 L-glutamic acid dimethyl ester 
• 56-86-0 L-glutamic acid 
• 607376-86-3 (S)-2-(tert-butoxycarbonylamino)pentane-1,5-diyl dimethanesulfonate 

Downstream Products

• 884602-81-7 (S)-tert-butyl 1-(2-nitro-4-(trifluoromethyl)phenyl)piperidin-3-ylcarbamate 
• 868609-86-3 (S)-1-(4-bromo-phenyl)-piperidin-3-ylamine 
• 876377-58-1 tert-butyl [(3S)-1-phenylpiperidin-3-yl]carbamate 
• 1056998-47-0 (3S)-1-[(3-Chloro-2-methylphenyl)sulfonyl]piperidin-3-amine hydrochloride 
• 1392490-59-3 (S)-[4-(3-acryloylamino-piperidine-1-sulfonyl)-phenyl]-carbamic acid benzyl ester 
• 1313376-63-4 Ethyl 2-(7-((S)-3-(4-chlorophenylsulfonamido)piperidin-1-yl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)pentanoate 
• 1313377-19-3 2-(7-((S)-3-(4-chlorophenylsulfonamido)piperidin-1-yl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)pentanoic acid 
• 1023298-99-8 (S)-1-(3-aminopyridin-4-yl)piperidin-3-yl-carbamic acid tert-butyl ester 
• 1611488-42-6 (S)-(3-aminopiperidin-1-yl)(3-methoxyphenyl)methanone 
• 1611487-78-5 (S)-(3-aminopiperidin-1-yl)(phenyl)methanone 
• 1611488-41-5 (S)-(3-aminopiperidin-1-yl)(4-methoxyphenyl)methanone 
• 1611488-43-7 (S)-(3-aminopiperidin-1-yl)(2-methoxyphenyl)methanone 

Relevant articles and documents

STEREOSELECTIVE SYNTHESIS OF PIPERIDINE DERIVATIVES

This invention relates to dialdehyde or dinitrile compounds, which are useful for stereoselective synthesis of piperidine, pyrrolidine, and azepane derivatives.

An efficient conversion of chiral α-amino acids to enantiomerically pure 3-amino cyclic amines

Enantiomerically pure 3-amino cyclic amines such as 3-amino pyrrolidine, 3-amino piperidine, and 2,3,4,5,6,7-hexahydro-1H-azepine have been synthesized in high yields from the optically active natural α-amino acids such as L-aspartic acid, L-glutamic acid, L-2-aminoadipic acid, and their enantiomers.