Benzyl chloroformate → 4-Amino-1-Cbz-piperidine-4-carboxylic acid

HRID 232011Notes

Reaction equation

HRID 232011 reaction equation
Br.[NH2:2][C:3]1([C:9]([OH:11])=[O:10])[CH2:8][CH2:7][NH:6][CH2:5][CH2:4]1.[C:12](Cl)([O:14][CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)=[O:13].[OH-].[Na+]>P([O-])(O)(O)=O.[K+].O.C1(C)C=CC=CC=1>[C:12]([N:6]1[CH2:7][CH2:8][C:3]([NH2:2])([C:9]([OH:11])=[O:10])[CH2:4][CH2:5]1)([O:14][CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)=[O:13]

Participants

7

Reactant 3

HCID 10387Benzyl chloroformateHCID 14798Sodium HydroxideHCID 200305764-Aminopiperidine-4-carboxylic acid hydrobromide

Product 1

HCID 145370764-Amino-1-Cbz-piperidine-4-carboxylic acidYield 50.3%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1140TolueneSolventHCID 516951Monobasic potassium phosphateSolvent

Conditions

Temperature
5 °C

Procedure

4-amino-4-carboxy-piperidine hydrobromide ([P. Jacobsen, K. Schaumburg, P. Krogsgaard-Larsen, Acta. Chem. Scandinavica B34, 319-326 (1980)]; 2.25 g, 10 mmoles) was dissolved in a solution of 18 ml potassium dihydrogen phosphate buffer (0.05 Molar potassium dihydrogen phosphate in 1N aqueous sodium hydroxide) and 6 ml of water. The solution was chilled with an ice-bath over an hour period during which solutions of carbobenzyloxy chloride (1.57 ml, 11 mmoles) in 3.0 ml of toluene and aqueous 1N sodium hydroxide were simultaneously added dropwise so as to maintain a pH of 7.0. The mixture was then stirred for one hour at 5° C., and for four additional hours at ambient temperature. The precipitate formed during the reaction was filtered and the filter cake washed with 3 (30 ml) portions of diethyl ether. The amorphous colorless solid was dried in vacuo affording 1.4 g of the title compound (50% yield). 1Hnmr (60 mHz; CF 3 CO2D) delta 2.0-2.7 (4H, broad m), 3.5-4.5 (4H, broad m), 5.28 (2H, s), 7.4 (5H, s).

Workup

  1. additionwere simultaneously added dropwise so as
  2. temperatureto maintain a pH of 7.0
  3. customat ambient temperature
  4. customThe precipitate formed during the reaction
  5. filtrationwas filtered
  6. washthe filter cake washed with 3 (30 ml) portions of diethyl ether
  7. customThe amorphous colorless solid was dried in vacuo

Sources & evidence

ORD record
ord-772e28005b0d48ce8ceaa8f9ae470f88
Source dataset
uspto-grants-1989_07
Patent number
US04851388

Reaction notes

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