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

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.

1. waitAfter 5 minutes
2. customthe dry ice/acetone bath was removed
3. additionThe reaction was then diluted with methylene chloride and water containing 5 mL of 2N hydrochloric acid
4. customthe layers were separated
5. washthe organic layers were washed with brine
6. dry with materialdried over sodium sulfate
7. customevaporated
8. customThe residue was purified by FC (10% ethyl acetate/hexanes)

ORD record

ord-0ff2243b252d4f738dcd22c74d5b8c7c

Source dataset

uspto-grants-2002_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06479518B2