Cyclohexanone → 8'-fluoro-5'-methoxy-1'H-spiro[cyclohexane-1,4'-quinazolin]-2'(3'H)-one

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of polyphosphoric acid (20 g) at 100° C. was added N-(2-fluoro-5-methoxyphenyl)urea (900 mg, 4.89 mmol) over 5 minutes followed by cyclohexanone (719 mg, 7.33 mmol) in one portion under N2. The mixture was stirred at 100° C. for 2 hours, cooled to 35° C. and quenched into water (400 mL). The crude product was filtered and washed with water (100 mL). The isolated solid was slurred in a mixture of tert-butylmethylether (8 mL) and ethyl acetate (4 mL) at 50° C. for 10 minutes, filtered, washed with tert-butylmethylether (10 mL) and dried in vacuo at 40° C. to give 8′-fluoro-5′-methoxy-1′H-spiro[cyclohexane-1,4′-quinazolin]-2′(3′H)-one (900 mg, 70%) as a light-brown solid, purity (97.3%).

Provenance & Evidence