Ammonium Chloride → (5R)-5-{(E)-2-(5-cyclopropyl-6-methoxypyridin-2-yl)-2-[4-(methylsulfanyl)phenyl]ethenyl}pyrrolidin-2-one

Participants

Reaction Conditions

Reaction Steps

A 1 M solution of lithiumhexamethyldisilazide in tetrahydrofuran (6.68 mL) was added to a solution of (5R)-5-{[(1-phenyl-1H-tetrazol-5-yl)sulfonyl]methyl}pyrrolidin-2-one obtained in Reference Example 3-2 (1.07 g) in tetrahydrofuran (10 mL) at −78° C. in a nitrogen gas stream, and the mixture was stirred at −78° C. for 30 minutes. A solution of (5-cyclopropyl-6-methoxypyridin-2-yl)[4-(methylsulfanyl)phenyl]methanone obtained in Reference Example 1-51 (500 mg) in tetrahydrofuran (10 mL) was added, and the mixture was stirred at −78° C. for one hour. The reaction solution was poured into a saturated ammonium chloride solution, followed by extraction with ethyl acetate. The organic layer was washed with saturated aqueous sodium bicarbonate and brine, dried over anhydrous magnesium sulfate and filtered. The solvent was then evaporated under reduced pressure. The residue was purified by silica gel column chromatography (chloroform:ethyl acetate=1:2) to give (5R)-5-{(E)-2-(5-cyclopropyl-6-methoxypyridin-2-yl)-2-[4-(methylsulfanyl)phenyl]ethenyl}pyrrolidin-2-one as a colorless oil (50.6 mg, 8%).

Provenance & Evidence