Hydrochloric Acid → 4,4-Difluoro-1-cyclohexyl-1,3-butanedione

Participants

Reaction Steps

To a stirred solution of cyclohexylmethylketone (2.52 g, 20 mmol) in DME (50 mL) at −20° C. was added ethyl difluoroacetate (7.44 g, 60 mmol) and sodium methoxide (6.48 g, 120 mmol), and the resulting reaction mixture was then stirred at room temperature for 1 hour. EtOAc (500 ml) and water (50 ml) were added, and the pH of the aqueous layer was adjusted to 6 by addition of 1 N HCl solution. The organic layer was washed with brine (50 ml), dried over Na2SO4, and concentrated in vacuo to give the title (3.8 g, 93%). This was used for the next coupling step without further purification.

Provenance & Evidence