Potassium carbonate hydrate → Apararenone

Participants

Reaction Conditions

Reaction Steps

N-[4-(4-fluorophenyl)-2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]-N-(methylsulfonyl)methanesulfonamide (8.5 g) was dissolved in dimethylsulfoxide (51 mL), a solution of potassium carbonate/water (7.98 g/8.5 mL) was added dropwise thereto at 25° C., and the mixture was stirred at the same temperature for 23 hours. To the reaction mixture was added dropwise concentrated hydrochloric acid/water (4.0 g/76.5 mL) at 30° C. or lower, then cooled to 20° C., and the mixture was stirred for 90 minutes. The precipitated crystals were collected by filtration, washed with water (76.5 mL), and then dried to obtain the title compound (6.40 g) as white crystals (Form B crystals). Subsequently, said crystals (6 g) were added to dimethylsulfoxide (21 mL), dissolved at about 50° C., then activated carbon (120 mg) and dimethylsulfoxide (3 mL) were added thereto, and stirred for 1 hour. After the mixture was filtered, to the filtrate at about 50° C. was added dropwise purified water (9 mL), and then stirred at the same temperature for 30 minutes. The mixture was cooled to 20° C., stirred for 1 hour, then the precipitated crystals were collected by filtration, and successively washed with purified water (54 mL) and ethanol (12 mL). The obtained crystals (6.57 g) were suspended in ethanol (30 mL), the suspension was heated under reflux for 2 hours, then cooled to 20° C., and stirred for 1 hour. The precipitated crystals were collected by filtration, and dried under reduced pressure at 50° C. to obtain the title compound (5.48 g) as crystals (Form A crystals) (yield: 83%, purity: 100%).

Provenance & Evidence