Triethyl phosphonoacetate → Ethyl 2-(diethoxyphosphoryl)-5-fluoropentanoate

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Reaction Steps

Sodium hydride (2.72 g, 60% on mineral oil, 68.0 mmol) was washed several times with hexanes under an nitrogen atmosphere and was then suspended in dry THF (60 mL). Ethyl (diethoxyphosphoryl)acetate (13.3 g, 59.1 mmol) was added dropwise within 20 min at r.t. as a solution in dry THF (20 mL). After stirring for 2 h at r.t. 1-bromo-3-fluoropropane (10.0 g, 70.9 mmol) was added and the mixture was heated to reflux for 14 h. The mixture was then cooled to r.t. and the reaction was quenched by addition of sat. aq. ammonium chloride solution (50 mL). The mixture was extracted with ethyl acetate (3×50 mL) and the combined organic layers were washed with brine and dried over sodium sulphate. After evaporation of the solvent under reduced pressure the crude product was purified by column chromatography (silica, hexanes/ethyl acetate gradient).

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