188111-79-7

Basic information

• Product Name: (R)-1-Boc-3-Aminopiperidine
• Synonyms: tert-Butyl (3R)-3-aminopiperidine-1-carboxylate;(R)-3-Aminopiperidine, N1-BOC protected;(R)-1-t-Butyloxycarbonyl-3-aminopiperidine hydrochloride;(R)-1-Boc-3-piperidinamine, tert-Butyl (R)-3-amino-1-piperidinecarboxylate;(3R)-3-Aminopiperidine, N1-BOC protected;(3R)-3-Amino-N1-Boc-piperidine;(R)-1-Boc-3-aMinopiperidi...;(R)-1-Boc-3-AMinopiperidin
• CAS NO: 188111-79-7
• Molecular Formula: C₁₀H₂₀N₂O₂
• Molecular Weight: 200.28
• EINECS: 1312995-182-4
• Product Categories: AMINOACID;pharmacetical;Piperidine;Piperidine Series;Piperidines;CHIRAL CHEMICALS
• Mol File: 188111-79-7.mol
• Article Data: 5

Chemical Properties

• Boiling Point: 277.3 °C at 760 mmHg
• Flash Point: 121.5 °C
• Appearance: Colorless to pale yellow/Liquid
• Density: 1.041g/cm3
• Vapor Pressure: 0.00456mmHg at 25°C
• Refractive Index: 1.4730
• Storage Temp.: Store under inert gas
• Solubility: Chloroform (Slightly), DMF (Slightly), DMSO (Slightly)
• PKA: 10.35±0.20(Predicted)
• Water Solubility: Immiscible with water.
• Sensitive: Moisture Sensitive
• CAS DataBase Reference: (R)-1-Boc-3-Aminopiperidine(CAS DataBase Reference)
• NIST Chemistry Reference: (R)-1-Boc-3-Aminopiperidine(188111-79-7)
• EPA Substance Registry System: (R)-1-Boc-3-Aminopiperidine(188111-79-7)

Safety Data

• Hazard Codes: Xn
• Statements: 22-36/37/38
• Safety Statements: 26
• RIDADR: UN2735
• WGK Germany: 3
• F: 10-34
• HazardClass: 8
• PackingGroup: III
• Hazardous Substances Data: 188111-79-7(Hazardous Substances Data)

Usage

Chemical Properties

Yellow liquid

Uses

Different sources of media describe the Uses of 188111-79-7 differently. You can refer to the following data:
1. (R)-(-)-3-Amino-1-Boc-piperidine is used as an intermediate in the manufacture of various substances such as pharmaceuticals.
2. (R)-3-Amino-1-Boc-piperidine can be used to prepare a benzoxazepine derivative named (R)-7-(3,5-dimethoxyphenyl)-N-(piperidin-3-yl)-4-propionyl-2,3,4,5-tetrahydro-1,4-benzoxazepine-9-carboxamide, a potent CBP/P300 bromodomain inhibitor.

General Description

(R)-3-Amino-1-Boc-piperidine can be used as a precursor for the preparation of dipeptidyl peptidase IV inhibitors like linagliptin, alogliptin, and other antidiabetic agents.

InChI:InChI=1/C10H20N2O2/c1-10(2,3)14-9(13)12-6-4-5-8(11)7-12/h8H,4-7,11H2,1-3H3/t8-/m0/s1

Synthetic route

tert-butyl (3R)-3-{[(benzyloxy)carbonyl]amino}piperidine-1-carboxylate (320580-76-5) → tert-butyl (3R)3-aminopiperidine-1-carboxylate (188111-79-7)

Conditions	Yield
Pd-C In methanol	99%

C10H18N2O2 → tert-butyl (3R)3-aminopiperidine-1-carboxylate (188111-79-7)

Conditions	Yield
With bis(1,5-cyclooctadiene)rhodium(I) tetrafluoroborate; C13H18FeP2; hydrogen; sodium hydride In dichloromethane Large scale;	95.2%

(R)-tert-butyl 3-carbamoylpiperidine-1-carboxylate (915226-43-6) → tert-butyl (3R)3-aminopiperidine-1-carboxylate (188111-79-7)

Conditions	Yield
With sodium hypochlorite; sodium hydroxide In water at 15 - 25℃; for 16h;	80%

3-oxo-piperidine-1-carboxylic acid tert-butyl ester (98977-36-7) → tert-butyl (3R)3-aminopiperidine-1-carboxylate (188111-79-7)

Conditions	Yield
With pyridoxal 5'-phosphate; immobilized Codex® amine ω-transaminase; isopropylamine In dimethyl sulfoxide at 50℃; pH=7.5; Temperature; Enzymatic reaction; enantioselective reaction;	70%
Multi-step reaction with 2 steps 1: ammonium acetate / ethanol / 7 h / Reflux; Large scale 2: bis(1,5-cyclooctadiene)rhodium(I) tetrafluoroborate; sodium hydride; C13H18FeP2; hydrogen / dichloromethane / Large scale View Scheme

tert-butyl (3R)3-aminopiperidine-1-carboxylate (188111-79-7) + 6-methylimidazo<2,1-b>thiazole-5-carboxylic acid (77628-51-4) → (R)-3-[(6-methyl-imidazo[2,1-b]thiazole-5-carbonyl)-amino]-piperidine-1-carboxylic acid tert-butyl ester (1030389-10-6)

Conditions	Yield
With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; for 20h;	100%
With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; for 20h;	100%

tert-butyl (3R)3-aminopiperidine-1-carboxylate (188111-79-7) + 3,5-dichloro-pyrazine-2-carbonitrile (313339-92-3) → tert-butyl (3R)-3-[(6-chloro-5-cyanopyrazin-2-yl)amino]piperidine-1-carboxylate (1207852-79-6)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; for 1h;	100%
With N-ethyl-N,N-diisopropylamine In butan-1-ol at 20 - 50℃;	60%

tert-butyl (3R)3-aminopiperidine-1-carboxylate (188111-79-7) + 3-(4-chloro-5-nitropyrimidin-2-yl)-6-fluoroimidazo[1,2-a]pyridine (1313279-53-6) → (R)-tert-butyl 3-(2-(6-fluoroimidazo[1,2-a]pyridin-3-yl)-5-nitropyrimidin-4-ylamino)piperidine-1-carboxylate (1313279-69-4)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 20℃;	100%

tert-butyl (3R)3-aminopiperidine-1-carboxylate (188111-79-7) + 2-chloroethyl isothiocyanate (1943-83-5) → tert-butyl (3R)-3-{[(2-chloroethyl)carbamoyl]amino}piperidine-1-carboxylate

Conditions	Yield
With triethylamine In dichloromethane for 4.41667h;	100%
With triethylamine In 4-(dicyanomethylene)-2-methyl-6-(p-dimethylaminostyryl)-4H-pyran at 20℃; for 4h;	81.5%

tert-butyl (3R)3-aminopiperidine-1-carboxylate (188111-79-7) + 4-methoxybenzoic acid (100-09-4) → (R)-tert-butyl 3-(4-methoxybenzamido)piperidine-1-carboxylate

Conditions	Yield
With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In 1,4-dioxane; N,N-dimethyl-formamide at 20℃; for 3h;	100%

tert-butyl (3R)3-aminopiperidine-1-carboxylate (188111-79-7) + 3-(4,6-dichloro-5-fluoropyrimidin-2-yl)pyrazolo[1,5-a]pyridine → tert-butyl (3R)-3-[(6-chloro-5-fluoro-2-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-4-yl)amino]piperidine-1-carboxylate

Conditions	Yield
With triethylamine In ethanol at 80℃; for 48h;	100%
With triethylamine In ethanol at 80℃; for 48h;	100%

tert-butyl (3R)3-aminopiperidine-1-carboxylate (188111-79-7) + 2-bromothiazole-5-carbonitrile (440100-94-7) → C14H20N4O2S

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 80℃; for 6h;	100%
With N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 80℃; for 6h;

tert-butyl (3R)3-aminopiperidine-1-carboxylate (188111-79-7) + N-(2-methoxypyridin-3-yl)-5-nitro-4-thiocyanatopyrimidin-2-amine (1414805-24-5) → (R)-tert-butyl 3-(2-(2-methoxypyridin-3-ylamino)-5-nitropyrimidin-4-ylamino)piperidine-1-carboxylate (1415151-88-0)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 50℃;	100%

tert-butyl (3R)3-aminopiperidine-1-carboxylate (188111-79-7) + 2-[(6-chloro-3-methyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-1-yl)methyl]-4-fluorobenzonitrile (865759-24-6) → C23H28FN5O4

Conditions	Yield
With sodium hydrogencarbonate In acetonitrile for 20h; Reflux;	99.2%

tert-butyl (3R)3-aminopiperidine-1-carboxylate (188111-79-7) + 3-(4,5-dichloropyrimidin-2-yl)-6-fluoroimidazo[1,2-a]pyridine (1313006-75-5) → tert-butyl (3R)-3-{[5-chloro-2-(6-fluoroimidazo[1,2-a]pyridin-3-yl)pyrimidin-4-yl]amino}piperidine-1-carboxylate (1313006-78-8)

Conditions	Yield
In ethanol for 18h; Reflux;	99%
In ethanol for 18h; Reflux;	99%

tert-butyl (3R)3-aminopiperidine-1-carboxylate (188111-79-7) → 3-(R)-aminopiperidine dihydrochloride (943528-10-7)

Conditions	Yield
With hydrogenchloride In ethanol for 2h; Large scale;	99%

tert-butyl (3R)3-aminopiperidine-1-carboxylate (188111-79-7) + 9-chloro-6-ethoxy-7-methoxy-1H,2H,3H-cyclopenta[b]quinoline → tert-butyl (3R)-3-({6-ethoxy-7-methoxy-1H,2H,3H-cyclopenta[b]quinolin-9-yl}amino)piperidine-1-carboxylate

Conditions	Yield
With chloro[2-(dicyclohexylphosphino)-3,6-dimethoxy-2′,4′,6′-tri-1-propyl-1,1′-biphenyl][2-(2-aminoethyl)phenyl]palladium(II); sodium t-butanolate In 1,4-dioxane at 110℃; for 2h; Buchwald-Hartwig Coupling;	99%

tert-butyl (3R)3-aminopiperidine-1-carboxylate (188111-79-7) + ethyl 2-methyl-5-chloropyrazolo[1,5-a]pyrimidine-3-carboxylate (1431654-56-6) → ethyl (R)-5-((1-(tert-butoxycarbonyl)piperidin-3-yl)amino)-2-methylpyrazolo[1,5-a]pyrimidine-3-carboxylate

Conditions	Yield
With potassium fluoride at 100℃; for 2h;	99%

tert-butyl (3R)3-aminopiperidine-1-carboxylate (188111-79-7) + ethyl 4-chloro-7H-pyrrolo[2,3-d]pyrimidine-5-carboxylate (144927-57-1) → C19H27N5O4

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In butan-1-ol at 135℃; for 1h; Sealed tube;	99%

tert-butyl (3R)3-aminopiperidine-1-carboxylate (188111-79-7) + (4,6-dichloropyrimidin-5-yl)(4-phenoxyphenyl)methanone → (R)-tert-butyl 3-((6-chloro-5-(4-phenoxybenzoyl)pyrimidin-4-yl)amino)piperidine-1-carboxylate

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In ethanol at 20℃; for 24h;	98.1%

tert-butyl (3R)3-aminopiperidine-1-carboxylate (188111-79-7) → 3-(R)-aminopiperidine dihydrochloride

Conditions	Yield
With hydrogenchloride In isopropyl alcohol	98%
With acetyl chloride In ethanol at 0 - 20℃;

tert-butyl (3R)3-aminopiperidine-1-carboxylate (188111-79-7) + 2,4-dichloro-7H-pyrrolo[2,3-d]pyrimidine (90213-66-4) → tert-butyl (R)-3-((2-chloro-7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)piperidine-1-carboxylate

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In ethanol at 110℃; for 12h;	98%

tert-butyl (3R)3-aminopiperidine-1-carboxylate (188111-79-7) + acryloyl chloride (814-68-6) → tert-butyl (3R)-3-(prop-2-Enoylamino)piperidine-1-carboxylate

Conditions	Yield
With triethylamine at 25℃; for 2h;	97.3%

tert-butyl (3R)3-aminopiperidine-1-carboxylate (188111-79-7) + methanol (67-56-1) + 1,1'-carbonyldiimidazole (530-62-1) → (R)-tert-butyl 3-((methoxycarbonyl)amino)piperidine-1-carboxylate

Conditions	Yield
Stage #1: methanol; 1,1'-carbonyldiimidazole With triethylamine In tetrahydrofuran at 20℃; for 0.166667h; Inert atmosphere; Stage #2: tert-butyl (3R)3-aminopiperidine-1-carboxylate In tetrahydrofuran at 75℃; for 12h;	97%

tert-butyl (3R)3-aminopiperidine-1-carboxylate (188111-79-7) + 9-chloro-6,7-bis(2H3)methoxy-1H,2H,3H-cyclopenta[b]quinoline → tert-butyl (3R)-3-{[6,7-bis(2H3)methoxy-1H,2H,3H-cyclopenta[b]quinolin-9-yl]amino}piperidine-1-carboxylate

Conditions	Yield
With chloro[2-(dicyclohexylphosphino)-3,6-dimethoxy-2′,4′,6′-tri-1-propyl-1,1′-biphenyl][2-(2-aminoethyl)phenyl]palladium(II); sodium t-butanolate In 1,4-dioxane at 100℃; for 1h; Buchwald-Hartwig Coupling; Sealed tube;	97%

tert-butyl (3R)3-aminopiperidine-1-carboxylate (188111-79-7) + (4,6-dichloropyrimidin-5-yl)(4-ethoxyphenyl)methanone → (R)-tert-butyl 3-((6-chloro-5-(4-ethoxybenzoyl)pyrimidin-4-yl)amino)piperidine-1-carboxylate

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In ethanol at 20℃; for 24h;	96%

tert-butyl (3R)3-aminopiperidine-1-carboxylate (188111-79-7) + 5,7-dichloro-3-iso-propyl-pyrazolo[1,5-a]pyrimidine (771510-32-8) → (R)-3-((5-chloro-3-isopropylpyrazolo[1,5-a]pyrimidin-7-yl)amino)piperidine-1-carboxylic acid tert-butyl ester

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In ethanol at 85℃;	96%

tert-butyl (3R)3-aminopiperidine-1-carboxylate (188111-79-7) + 3-(4,6-dichloropyrimidin-2-yl)pyrazolo[1,5-a]pyridine → tert-butyl (3R)-3-[(6-chloro-2-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-4-yl)amino]piperidine-1-carboxylate

Conditions	Yield
With triethylamine In ethanol for 64h; Reflux;	95%

tert-butyl (3R)3-aminopiperidine-1-carboxylate (188111-79-7) + 1H-pyrazole-1-carboximidamide hydrochloride (4023-02-3) → tert-butyl (3R)-3-{[(Z)-amino(imino)methyl]amino}piperidine-1-carboxylate hydrochloride (885049-13-8)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 60℃; for 6h;	94%

tert-butyl (3R)3-aminopiperidine-1-carboxylate (188111-79-7) + 1H-pyrazole-1-carboximidamide hydrochloride (4023-02-3) → tert-butyl (3R)-3-{[amino(imino)methyl]amino}piperidine-1-carboxylate hydrochloride

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 70℃; for 18h;	94%

tert-butyl (3R)3-aminopiperidine-1-carboxylate (188111-79-7) + 5-bromo-2-(tetrahydro-2H-pyran-2-yl)-2H-indazole (1178903-21-3) + 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl (76144-87-1, 76189-55-4, 76189-56-5, 136655-44-2, 98327-87-8) → (R)-tert-butyl 3-(phenylamino)piperidine-1-carboxylate (1178903-50-8) + (3R)-tert-butyl 3-(2-(tetrahydro-2H-pyran-2-yl)-2H-indazol-5-ylamino)piperidine-1-carboxylate (1178903-52-0)

Conditions	Yield
With tris-(dibenzylideneacetone)dipalladium(0); sodium t-butanolate In tetrahydrofuran at 55℃; for 18h; Buchwald coupling; Inert atmosphere;	A n/a B 94%

tert-butyl (3R)3-aminopiperidine-1-carboxylate (188111-79-7) + 7-chloro-1-methyl-1H-pyrrolo[2,3-c]pyridine (875340-57-1) → (R)-tert-butyl 3-((1-methyl-1H-pyrrolo[2,3-c]pyridin-7-yl)amino)piperidine-1-carboxylate

Conditions	Yield
With tris-(dibenzylideneacetone)dipalladium(0); dicyclohexyl-(2′,4′,6′-triisopropyl-3,6-dimethoxy-[1,1′-biphenyl]-2-yl)phosphine; sodium t-butanolate In toluene at 105℃; for 3h; Inert atmosphere;	94%

tert-butyl (3R)3-aminopiperidine-1-carboxylate (188111-79-7) + 4-bromo-2-nitrobenzoic acid (99277-71-1) → (R)-tert-butyl 3-(4-bromo-2-nitrobenzamido)piperidine-1-carboxylate

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 10 - 35℃; for 4h;	94%

Upstream product

• 98977-36-7 3-oxo-piperidine-1-carboxylic acid tert-butyl ester 
• 915226-43-6 (R)-tert-butyl 3-carbamoylpiperidine-1-carboxylate 
• 320580-76-5 tert-butyl (3R)-3-{[(benzyloxy)carbonyl]amino}piperidine-1-carboxylate 

Downstream Products

• 1062132-47-1 (R)-tert-butyl 3-(4-tert-butylbenzamido)piperidine-1-carboxylate 
• 334618-23-4 3-(R)-aminopiperidine dihydrochloride 

Relevant articles and documents

Asymmetric synthesis of a high added value chiral amine using immobilized ω-transaminases

Chiral N-heterocyclic molecules and in particular compounds with an amino functional group such as 3-aminopiperidine are valuable intermediates for the production of a large number of bioactive compounds with pharmacological properties. In this paper, the synthesis of both enantiomers of 3-amino-1-Boc-piperidine by amination of the prochiral precursor 1-Boc-3-piperidone using immobilized ω-transaminases (TAs-IMB), isopropylamine as amine donor and pyridoxal-5’-phosphate (PLP) as cofactor is described. Compared to other methods, the present approach affords the target compound in just one step with high yield and high enantiomeric excess starting from a commercial substrate. The reaction was carried out by using different commercially available immobilized enzymes, evaluating the catalytic activity and the enantioselectivity under different experimental conditions. Re-use of the most efficient enzyme was performed both in batch and in a semi-continuous system. The selected biocatalyst showed good stability under the reaction conditions providing consistent results in terms of conversion and enantiomeric excess after several cycles. The reported results may be of practical interest in view of the development of this sustainable approach to an industrial scale.

METHOD FOR PRODUCING OPTICALLY ACTIVE 3-AMINOPIPERIDINE OR SALT THEREOF

The present invention relates to a method for producing an optically active 3-aminopiperidine or salt thereof. In the method, a racemic nipecotamide is stereoselectively hydrolyzed to obtain an optically active nipecotamide and an optically active nipecotic acid in the presence of an enzyme source derived from an organism, and then the optically active nipecotamide is derived into an optically active aminopiperidine or salt thereof by aroylation, Hofmann rearrangement, deprotection of the amino group and further deprotection; or the optically active nipecotamide is derived into an optically active aminopiperidine or salt thereof by selective protection with BOC, Hofmann rearrangement and further deprotection. It is possible by the present invention to produce an optically active 3-aminopiperidine or salt thereof useful as a pharmaceutical intermediate from an inexpensive and easily available starting material by easy method applicable to industrial manufacturing.

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