Tetrahydrofuran → 2-[(S)-1-{(3aS,7E,7aR)-7-(bromomethylene)-3a,4,5,6,7,7a-hexahydro-3a-methyl-1H-indene-3-yl}ethoxy]-N-(2,2,3,3,3-pentafluoropropyl)acetamide

Participants

Reaction Conditions

Reaction Steps

Under a nitrogen atmosphere, a solution of sodium hexamethyldisilazide in tetrahydrofuran (1.1 M, 5.31 ml, 5.84 mmol) was cooled to −15° C., and a solution of (S)-1-{(3aS,7E,7aR)-7-(bromomethylene)-3a,4,5,6,7,7a-hexahydro-3a-methyl-1H-indene-3-yl}ethanol (Compound 5: 633.7 mg, 2.337 mmol) in dimethylformamide (1 ml) was added thereto over 4 minutes. The resulting mixture was stirred at −15° C. for 7 minutes, and a solution of 2-bromo-N-(2,2,3,3,3-pentafluoropropyl)acetamide (726 mg, 2.688 mmol) in dimethylformamide (1 ml) was added thereto over 5 minutes. After stirring the reaction solution at −5° C. for 30 minutes, aqueous ammonium chloride solution (5 ml) and hexane (20 ml) were added thereto, and the separation of the solution was conducted. The obtained organic layer was sequentially washed with water (5 ml) and saturated brine (4 ml)/water (1 ml), and the solvent was evaporated. The obtained crude product was purified by silica gel column chromatography to obtain 2-[(S)-1-{(3aS,7E,7aR)-7-(bromomethylene)-3a,4,5,6,7,7a-hexahydro-3a-methyl-1H-indene-3-yl}ethoxy]-N-(2,2,3,3,3-pentafluoropropyl)acetamide (1.08 g, quantitatively).

Provenance & Evidence