Dimethyl Sulfoxide → HCID 25209257, compound

Participants

Reaction Conditions

Reaction Steps

A solution of oxalyl chloride (57.0 ml, 653 mmol) in dichloromethane (635 ml) was cooled in a dry ice-methanol bath. Dimethylsulfoxide (92.7 ml, 1306 mmol) was added drop wise and the solution was stirred for 30 minutes. A solution of benzyl 7-[(1R,2R,3R,5S)-2-(4,4-difluoro-3-hydroxyoctyl)-5-hydroxy-3-(2-tetrahydropyranyloxy)cyclopentyl]heptanate (18) (74.31 g, 130.7 mmol) in dichloromethane (191 ml) was added drop wise, and the mixture was stirred for approximately 1.5 hours. Triethylamine (273 ml, 1959 mmol) was added drop wise to the mixture and the reaction mixture was warmed to 0° C., saturated ammonium water (605 ml) was added to the solution and the mixture was stirred, let to stand and then separated into two layers. The aqueous layer was extracted twice with dichloromethane (302 ml). The organic layers were combined and sequentially washed with 0.35N-hydrochloric acid (302 ml), water (605 ml), saturated sodium bicarbonate water (605 ml) and saturated aqueous sodium chloride (605 ml). After drying with anhydrous magnesium sulfate (52 g), the solution was concentrated under reduced pressure. The residue was dissolved in a suitable amount of ethyl acetate/hexane solvent mix (1:10), and insoluble matter was filtered. The filtrate was concentrated under reduced pressure and the residue was purified by silica gel column chromatography (Fuji Silysia BW-300: 2260 g; ethyl acetate:hexane=1:4) to give benzyl 7-[(1R,2R,3R)-2-(4,4-difluoro-3-oxooctyl)-5-oxo-3-(2-tetrahydropyranyloxy)cyclopentyl]heptanate (19) (71.44 g; 126.5 mmol; yield: 96.8%) as a pale yellow oil.

Provenance & Evidence