Benzaldehyde → Methyl (3S)-3-hydroxy-3-phenylpropanoate

Participants

Reaction Conditions

Reaction Steps

At room temperature, a three-neck flask equipped with a reflux condenser, internal thermometer, dropping funnel and stirrer under protective nitrogen gas was initially charged with 5 g of zinc dust (77 mmol) in 30 ml of tetrahydrofuran. After 1.2 ml of trimethylchlorosilane had been added, the mixture was heated to 55 C for 15 min, and 10.9 g of methyl bromoacetate (71 mmol) were subsequently added dropwise undiluted while refluxing at 45° C. within 7 min. The mixture was then stirred for 10 min. After cooling to 10 C, 30 ml of tetrahydrofuran were added and 17 g of (−)-sparteine (72 mmol) were subsequently added undiluted at 0 C, and the temperature rose to 5 C. The mixture was cooled to 15 C and 6.4 g of benzaldehyde (60 mmol) were added undiluted. The reaction mixture was subsequently stirred at 15 C for 20 h, then acidified at this temperature with 35 ml of 20% hydrochloric acid to a pH of 3 and stirred for 10 min, and the temperature of the mixture rose to 0 C. 150 ml of water were then added. Precipitated sparteine salt was filtered off with suction and washed twice with 40 ml of ethyl acetate each time. After removing the organic phase, the aqueous phase was extracted with 50 ml of ethyl acetate and the organic phase was subsequently removed. The organic phase was then stirred with 20 ml of concentrated ammonia solution at −10° C. for 5 min. After phase separation, drying and removal of solvent under reduced pressure, methyl (S)-(−)-3-hydroxy-3-phenylpropionate was obtained in a yield of 10.5 g (97% of theory) and a purity of >95% and 89% ee (HPLC).

Provenance & Evidence