Dimethyl Sulfoxide → 1-(S)-(1-(R)-(3,5-Bis(trifluoromethyl)phenyl)ethoxy)-2-(R)-(4-fluorophenyl)-3-(R)-(formyl)cyclopentane

Participants

Reaction Steps

To a solution of 0.248 mL of oxalyl chloride in 8 mL of methylene chloride cooled to −70° C. was added dropwise 0.40 ml of DMSO. The reaction was stirred for 10-15 minutes and then a solution of 510 mg of 1-(S)-(1-(R)-(3,5-bis(trifluoromethyl)phenyl)ethoxy)-2-(R)-(4-fluorophenyl)-3-(R)-(hydroxymethyl)-cyclopentane from Example 19, Method A or B in 5 mL of methylene chloride was added dropwise at −70° C. The reaction was stirred for 1 hour before dropwise addition of 2.0 mL of DIPEA in 3 mL of methylene chloride. After 5 minutes, the dry ice/acetone bath was removed and the reaction was allowed to warm to room temperature over 1 hour. The reaction was then diluted with methylene chloride and water containing 5 mL of 2N hydrochloric acid and the layers were separated. The aqueous layer was reextracted with methylene chloride and the organic layers were washed with brine, dried over sodium sulfate, combined and evaporated. The residue was purified by FC (10% ethyl acetate/hexanes) to give 440 mg of title compound as a waxy solid.

Provenance & Evidence