Triethyl phosphonoacetate → Ethyl 3-(3,5-difluorophenyl)propanoate

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Reaction Conditions

Reaction Steps

Dimethoxyethane 350 ml was added to 60% sodium hydride 14.4 g (360 mmol), the mixture was stirred at room temperature while a solution of ethyl diethylphosphonoacetate 80.7 g (360 mmol) in dimethoxyethane (50 ml) was added dropwise. After the generation of hydrogen gas was stopped, the solution was cooled to 15° C., and a solution of 3,5-difluorobenzaldehyde 50.0 g (352 mmol) in dimethoxy ethane (50 ml) was added dropwise keeping the liquid temperature below 25° C. After addition, the mixture was stirred for 30 minutes, the reactant was added to water 300 ml, and the product was extracted with diethylether. The extract was washed with a sodium chloride aqueous solution, and dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (eluent: heptane/ethyl acetate=3/1). Such obtained purified material was hydrogenated in the presence of 5% palladium carbon as a catalyst in ethanol 300 ml. After hydrogenation, the catalyst was filtered off, the solvent was distilled off under reduced pressure to obtain 3-(3,5-difluorophenyl) propionic acid ethyl ester 53.0 g (247 mmol). The yield was 70.2% from 3,5-difluorobenzaldehyde.

Provenance & Evidence