2,2,2-Trichloroethyl chloroformate → rac-(3R,4S)-3-(3,4-dichloro-phenyl)-4-[(4-methoxy-3-trifluoromethyl-benzoyl)-methyl-amino]-pyrrolidine-1-carboxylic acid 2,2,2-trichloro-ethyl ester

HRID 1951063Notes

Reaction equation

HRID 1951063 reaction equation
C([N:8]1[CH2:12][C@@H:11]([C:13]2[CH:18]=[CH:17][C:16]([Cl:19])=[C:15]([Cl:20])[CH:14]=2)[C@H:10]([N:21]([CH3:36])[C:22](=[O:35])[C:23]2[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[C:25]([C:31]([F:34])([F:33])[F:32])[CH:24]=2)[CH2:9]1)C1C=CC=CC=1.Cl[C:38]([O:40][CH2:41][C:42]([Cl:45])([Cl:44])[Cl:43])=[O:39]>CC#N>[Cl:43][C:42]([Cl:45])([Cl:44])[CH2:41][O:40][C:38]([N:8]1[CH2:9][CH:10]([N:21]([C:22](=[O:35])[C:23]2[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[C:25]([C:31]([F:34])([F:33])[F:32])[CH:24]=2)[CH3:36])[CH:11]([C:13]2[CH:18]=[CH:17][C:16]([Cl:19])=[C:15]([Cl:20])[CH:14]=2)[CH2:12]1)=[O:39]

Participants

4

Reactant 2

HCID 870632,2,2-Trichloroethyl chloroformateHCID 67025727Rac-n-[(3s,4r)-1-benzyl-4-(3,4-dichloro-phenyl)-pyrrolidin-3-yl]-4-methoxy-n-methyl-3-trifluoromethyl-benzamide

Product 1

HCID 87634196rac-(3R,4S)-3-(3,4-dichloro-phenyl)-4-[(4-methoxy-3-trifluoromethyl-benzoyl)-methyl-amino]-pyrrolidine-1-carboxylic acid 2,2,2-trichloro-ethyl ester

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a stirred solution of rac-N-[(3S,4R)-1-benzyl-4-(3,4-dichloro-phenyl)-pyrrolidin-3-yl]-4-methoxy-N-methyl-3-trifluoromethyl-benzamide (1.10 g, 2.05 mmol) in CH3CN (15 ml) at RT was added 2,2,2-trichloroethyl chloroformate (0.56 ml, 4.10 mmol) in two portions (within 30 min.). The reaction mixture was stirred an additional 2 hours, concentrated under vacuo, and then filtrated on silica gel (CH2Cl2 as solvent) to afford the intermediate rac-(3R,4S)-3-(3,4-dichloro-phenyl)-4-[(4-methoxy-3-trifluoromethyl-benzoyl)-methyl-amino]-pyrrolidine-1-carboxylic acid 2,2,2-trichloro-ethyl ester. This intermediate was then dissolved in AcOH (10 ml) and zinc powder (300 mg) was added in 4 portions over 3 hours. The reaction mixture was then filtered on celite, concentrated under vacuo, taken up in CH2Cl2, and washed with aq. NaHCO3. The organic phases were dried over Na2SO4, and purification by flash chromatography (SiO2, CH2Cl2/MeOH, 90:10) yielded 0.45 g (50%) of the title product as colorless oil. ES-MS m/e: 447.1 (M+H+).

Workup

  1. concentrationconcentrated under vacuo
  2. filtrationfiltrated on silica gel (CH2Cl2 as solvent)

Sources & evidence

ORD record
ord-d5cf993173174432a7acec2279c39266
Source dataset
uspto-grants-2013_03
Patent number
US08404679B2

Reaction notes

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