Acetic Acid → 3-chloro-2(R)-hydroxy-propyl(cyclohexylmethyl)phosphinic acid ethyl ester

Participants

Reaction Steps

20.0 g of cyclohexylmethylphosphinic acid ethyl ester are dissolved in 150 ml of tetrahydrofuran, and at 0° 11.0 g of triethylamine and then, dropwise, 12.0 g of trimethylchlorosilane are added, a white precipitate being formed. The resulting suspension is stirred at room temperature for 24 hours and then filtered under argon. The filtrate is concentrated by evaporation under reduced pressure. 10.9 g of (R)-epichlorohydrin and 2.0 g of anhydrous zinc chloride are added to the residue. When the exothermic reaction has died away, the mixture is heated under reflux at 60° for a further 24 hours. The reaction mixture is allowed to cool to room temperature, diluted with dichloromethane and washed with water. The organic phase is separated off, dried over sodium sulfate and concentrated by evaporation. The residue is dissolved in dichloromethane and washed with water. Drying over sodium sulfate and concentration by evaporation yield an oil. The oil is taken up in % methanolic acetic acid, left to stand at room temperature for 24 hours and then concentrated by evaporation. The residue is purified by chromatography on silica gel, yielding 3-chloro-2(R)-hydroxy-propyl(cyclohexylmethyl)phosphinic acid ethyl ester; 1H-NMR spectrum (in CDCl3): δ=4.47 (1H,d), 4.21-4.02 (3H,m), 3.6 (2H,m), 2.11-1.54 (9H,m), 1.38-0.97 (9H,m).

Provenance & Evidence