4-Methylmorpholine → 2-(2-Oxo-2-phenyl-ethylcarbamoyl)-piperidine-1-carboxylic acid benzyl ester

HRID 1443382Notes

Reaction equation

HRID 1443382 reaction equation
[C:1]([N:11]1[CH2:16][CH2:15][CH2:14][CH2:13][C@H:12]1[C:17]([OH:19])=O)([O:3][CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:2].Cl.[NH2:21][CH2:22][C:23]([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)=[O:24].ON1C2C=CC=CC=2N=N1.CN(C)CCCCN=C=NCC.CN1CCOCC1>ClCCl.O>[CH2:4]([O:3][C:1]([N:11]1[CH2:16][CH2:15][CH2:14][CH2:13][CH:12]1[C:17](=[O:19])[NH:21][CH2:22][C:23](=[O:24])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)=[O:2])[C:5]1[CH:6]=[CH:7][CH:8]=[CH:9][CH:10]=1

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 688345(S)-1-N-Cbz-Pipecolinic acidHCID 2723597Ethanone, 2-amino-1-phenyl-, hydrochloride (1:1)HCID 21914090(4-Dimethylamino-butyl)-ethyl-carbodiimide

Product 1

HCID 235707182-(2-Oxo-2-phenyl-ethylcarbamoyl)-piperidine-1-carboxylic acid benzyl ester

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

(S)-1-(Carbobenzyloxy)-2-piperidinecarboxylic acid (15.8 g, 60 mmol), 2-amino-1phenyl-ethanone hydrochloride (10.30 g, 60 mmol), and HOBT (1-hydroxybenzo-triazole) (16.20 g, 120 mmol) were mixed in dichloromethane (400 mL). The stirring mixture was cooled to 0° C. and then (4-dimethylamino-butyl)-ethyl-carbodiimide (14.90 g, 78 mmol) and NMM (N-methyl-morpholine) (7.27 g, 72 mmol) were added. The reaction mixture was then warmed to room temperature. After 16 hours the reaction mixture was treated with water, and the resulting solid was filtered. The organic phase from the filtrate was separated and washed consecutively with saturated NaHCO3, 2N citric acid, and saturated NaHCO3 once again, then dried over MgSO4, filtered, and concentrated to yield the title product 2-(2-oxo-2-phenyl-ethylcarbamoyl)-piperidine-1-carboxylic acid benzyl ester as a yellow oil, which was used without further purification.

Workup

  1. temperatureThe reaction mixture was then warmed to room temperature
  2. filtrationthe resulting solid was filtered
  3. customThe organic phase from the filtrate was separated
  4. washwashed consecutively with saturated NaHCO3, 2N citric acid, and saturated NaHCO3 once again
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-77b5c372e3ad4cb5b045d9fa870f3067
Source dataset
uspto-grants-2010_02
Patent number
US07659402B2

Reaction notes

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