Acetic Acid → [(4S)-4-Methyl-2-oxooctyl]phosphonic acid dimethyl ester

Participants

Reaction Steps

To a solution of dimethyl methylphosphonate (32.5 g, 0.262 mol) in anhydrous THF (480 ml) was dropwise added 1.63N n-butyl lithium (160 ml, 0.261 mol) at -78° C. After stirring for 30 minutes, a solution of methyl l-3-methylheptanoate (16.5 g, 0.104 mol) in anhydrous THF (25 ml) was added dropwise, and the mixture was stirred at -78° C. for one hour and at room temperature for 2 hours. Acetic acid (19 ml) and water (100 ml) were added to the reaction mixture. After distilling off THF, the residue was extracted with ether (500 ml×3). The combined organic layers were washed with brine (250 ml×2), dried over anhydrous sodium sulfate, and concentrated. The residue was distilled under reduced pressure to give dimethyl (4S)-4-methyl-2-oxo-octylphosphonate (23.6 g, 0.094 mol, 90%, b.p.=124°-125° C./0.5 mmHg). The structure was confirmed by the following data.

Provenance & Evidence