Phosphate → HCID 22007157, compound

Participants

Reaction Steps

2.86 g (9.3 mmol) of (±)-α-chloromethyl-2-methoxy-5-sulphamoylbenzyl acetate and 110 ml of t-butyl methyl ether are introduced into a 500-ml three-necked flask. The mixture is stirred for 15 minutes, 170 ml of phosphate buffer are then added and the mixture is stirred vigorously until an emulsion is obtained. 0.57 g (20%) of lipase SP 523 is then added and the reaction is monitored at room temperature using a pH-stat (addition of 1M sodium hydroxide) and by HPLC on a chiral column, and the degree of conversion of the ester and the enantiomeric excesses of the ester and of the alcohol are determined. After 45 hours of reaction, when the enantiomeric excesses of the ester and of the alcohol are greater than 95%, the reaction medium is diluted with 800 ml of ethyl acetate, the organic phase is separated and the aqueous phase is re-extracted with 3 times 500 ml of ethyl acetate. The organic phases are combined, dried and concentrated, and the residue is purified by 2 successive flash chromatographic runs on a silica column with a 30:70 mixture of ethyl acetate and cyclohexane. 1.32 g of (−)-α-chloromethyl-2-methoxy-5-sulphamoylbenzyl acetate (ee=99%) and 1.05 g of (+)-α-chloromethyl-2-methoxy-5-sulphamoylbenzenemethanol are obtained.

Provenance & Evidence