Diisopropylamine → HCID 59570922, compound

Participants

Reaction Conditions

Reaction Steps

To a mixture of diisopropylamine (6.94 mL), 1,3-dimethyltetrahydropyrimidin-2(1H)-one (18 mL) and THF (60 mL) was added 2.64 M n-butyl lithium/hexane solution (18.4 mL) at an internal temperature of −50° C. or lower, followed by stirring at an internal temperature of −50° C. or lower for 1 hour. To the reaction mixture was added dropwise a solution of methyl [3-bromo-4-(cyclopropylsulfonyl)phenyl]acetate (15.0 g) in THF (20 mL)/1,3-dimethyl tetrahydropyrimidin-2(1H)-one (9 mL) at an internal temperature of −50° C. or lower, followed by stirring at the same temperature for 30 minutes, and THF (30 mL) was added thereto, followed by stirring at −20° C. for 1 hour. A solution of (2R,3R,7S)-7-(iodomethyl)-2,3-diphenyl-1,4-dioxaspiro[4.4]nonane (21.8 g) in THF (20 mL) was added dropwise thereto at an internal temperature of −60° C. or lower, followed by stirring at the same temperature for 30 minutes and then stirring at room temperature overnight. To the reaction mixture was added water (200 mL) under ice-cooling, followed by extraction with ethyl acetate (100 mL×3). The organic layer was sequentially washed with water (200 mL) and saturated brine (200 mL), and dried over anhydrous magnesium sulfate, and the solvent was then evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate 19:1→1:1) to obtain methyl 2-[3-bromo-4-(cyclopropylsulfonyl)phenyl]-3-[(2R,3R,7R)-2,3-diphenyl-1,4-dioxaspiro[4.4]non-7-yl]propionate (20.4 g) as a pale yellow amorphous substance.

Provenance & Evidence