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

Participants

Reaction Conditions

Reaction Steps

To a solution of 5.4 mL (61.7 mmole) of oxalyl chloride in 100 mL of methylene chloride cooled to −70° C. was added dropwise 8.7 mL (123 mmole) of DMSO. The reaction was stirred for 10-15 minutes at −70° C. and then a solution of 11.11 g (24.7 mmole) of 1-(S)-(1-(R)-(3,5-bis(trifluoromethyl)phenyl)ethoxy)-2-(R)-(4-fluorophenyl)-3-(R)-(hydroxymethyl)cyclopentane, prepared as in Example 19, Step A, in 40 mL of methylene chloride was added dropwise at −70° C. The reaction was stirred for 1 hour before dropwise addition of 43 mL (246 mmole) of DIPEA in 25 mL of methylene chloride. After 5 minutes, the dry ice/acetone bath was removed and the reaction was warmed to room temperature in a water bath and stirred for 1 hour. The reaction was then diluted with methylene chloride and water containing 150 mL of 2N hydrochloric acid and the layers were separated. The aqueous layer was reextracted with methylene chloride and the organic layers were each washed with a portion of brine, dried over sodium sulfate, combined and evaporated. The residue was purified by FC (10% ethyl acetate/hexanes) to give 9.8 g of title compound as a waxy solid.

Provenance & Evidence