Acetic Acid → HCID 57809776, compound

Participants

Reaction Steps

To a solution of the difluoromethylphosphonic acid diethyl ester (1.35 g) in THF (5.0 mL) cooled in a dry ice/acetone bath was added LDA (5.0 mL, 1.5M in cyclohexane) dropwise over 5.0 minutes. After 10.0 minutes, a solution of 3-methyl-3-(2-methoxy-5-fluorophenyl)butyraldehyde (0.94 g) in THF (5.0 mL) was added dropwise. After an additional 20.0 minutes, acetic acid (1 mL) was added and the mixture was warmed to room temperature. The mixture was diluted with ethyl acetate, washed with water, dried, filtered, and evaporated in vacuo. Fractionation of the residue over silica gel (eluent: methylene chloride-ethyl acetate (1:4)) gave the desired [1,1-difluoro-4-(5-fluoro-2-methoxyphenyl)-2-hydroxy-4-methylpentyl]phosphonic acid diethyl ester (1.15 g, 40%) as an oil that crystallized on treatment with hexanes.

Provenance & Evidence