6-Fluoro-4-chromanone hydantoin → 4-Amino-6-fluoro-3,4-dihydro-2H-1-benzopyran-4-carboxylic acid

Participants

Reaction Conditions

Reaction Steps

A stirred slurry of 78 g (0.33 mole) of (RS)-6-fluoro-spiro-[chroman-4,4'-imidazolidine]-2',5'-dione and 208.3 g (0.66 mole) of barium hydroxide octahydrate in 585 ml of water was slowly heated to reflux over 3 hours and refluxed 16 hours. The slurry was cooled to 80° C. and powdered NH4CO3 (78 g) added portionwise over 5 minutes. Moderate foaming was noted. After stirring 1.5 hours at 80° C., the mixture was cooled to 60° C., and filtered over diatomaceous earth with 2×100 ml hot water for wash. The combined filtrate and washes were stripped to 200 ml and allowed to stand overnight. 2-Propanol (600 ml) was added and the mixture heated to 70° C. to dissolve precipitated solids. The hot solution was treated with activated carbon, filtered over diatomaceous earth and washed with hot 1:1 water:2-propanol. The combined filtrate and washes were stripped to 200 ml, and water chased with 3×300 ml fresh 2-propanol. The resulting thick slurry was diluted with 200 ml additional 2-propanol, cooled to 5° C., granulated for 0.5 hour, filtered and air dried to yield title product, 63.5 g, 91.2%, mp 252°-253° C. (dec).

Provenance & Evidence