Toluene → N-[(S)-alpha-methylbenzyl]-(RS)-proline methyl ester

HRID 565721Notes

Reaction equation

HRID 565721 reaction equation
Br[CH:2]([CH2:7][CH2:8][CH2:9]Br)[C:3]([O:5][CH3:6])=[O:4].C1(C)C=CC=CC=1.C(=O)([O-])[O-].[K+].[K+].[CH3:24][C@H:25]([NH2:32])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1>O>[CH3:6][O:5][C:3](=[O:4])[CH:2]1[CH2:7][CH2:8][CH2:9][N:32]1[C@@H:25]([CH3:24])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1

Participants

6

Reactant 4

HCID 1140TolueneHCID 11430Potassium CarbonateHCID 758181-Phenethylamine, (-)-HCID 10912698Methyl 2,5-dibromopentanoate

Product 1

HCID 11160639N-[(S)-alpha-methylbenzyl]-(RS)-proline methyl esterYield 78.1%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

Methyl (RS)-2,5-dibromovalerate (24.5 g) and toluene (19.8 g) were added to a 49% aqueous potassium carbonate solution (53.3 g), and heated to 80° C. (S)-α-methylbenzylamine (12.0 g) was added dropwise to the mixture obtained above at that temperature, and was stirred at that temperature for 9.5 hours. Water (33.9 g) was added to the reaction mixture, and then the organic layer was separated from the resulting mixture. Separated organic layer was washed with water, a 1% aqueous hydrochloric acid solution and water in this order, and concentrated under reduced pressure. Thus, N-[(S)-α-methylbenzyl]-(RS)-proline methyl ester (16.3 g) was obtained in a yield of 77.8%.

Workup

  1. additionwas added dropwise to the mixture
  2. customobtained above at that temperature
  3. customthe organic layer was separated from the resulting mixture
  4. washSeparated organic layer was washed with water
  5. concentrationa 1% aqueous hydrochloric acid solution and water in this order, and concentrated under reduced pressure

Sources & evidence

ORD record
ord-7af25a2137c0452f8a652c5f117e123a
Source dataset
uspto-grants-2001_01
Patent number
US06172234B2

Reaction notes

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