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

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Reaction Steps

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+).

Provenance & Evidence