Pyrrolidine → 7-Chloro-2-(difluoromethyl)-2-methylchroman-4-one

Participants

Reaction Steps

1-(4-Chloro-2-hydroxyphenyl)ethanone (8.07 g, 47.3 mmol), MeOH (81 mL), 1,1-difluoroacetone (4.89 g, 52.0 mmol), and pyrrolidine (4.30 ml, 52.0 mmol) were stirred at ambient temperature for 45 hours, at 35° C. for 7 hours, then at 50° C. for 3 hours. The reaction mixture was concentrated, diluted with MTBE (75 mL), then washed with water (40 mL), 2N HCl (2×25 mL), brine (20 mL), 2N NaOH (2×20 mL), and brine (2×20 mL). The organic portion was dried (Na2SO4), filtered, and concentrated to give the title compound (9.78 g, 39.7 mmol, 84%) as a brown oil. MS (DCI/NH3) m/z 264 (M+NH4)+.

Provenance & Evidence