Sodium Hydroxide → (R)-1-(4-hydroxyphenyl)-5-oxo-pyrrolidine-3-carboxylic acid methyl ester

Participants

Reaction Steps

A suspension of 2.51 g (10.6 mmol) of (RS)-1-(4-hydroxy-phenyl)-5-oxo-pyrrolidine-3-carboxylic acid methyl ester in 10 ml of phosphate buffer [c(KH2PO4)=0.05 mol/l], 25 ml of sodium sulfate solution [c(Na2SO4)=4 mol/l], 45 ml of deionised water, and 20 ml of tert-butylmethylether is adjusted to pH 6.0. Under moderate stirring, 51.3 mg of cholesterase from Candida cylindracea (Roche Applied Science, Industrial Products, Enzyme Projects, Sandhofer Str. 116, D-68305 Mannheim, Germany, order no. 10129046103) are added in solid form. By an automatic pH-Stat-System, the pH is kept constant at 6.0 by addition of sodium hydroxide solution [c(NaOH)=1.0 mol/l] at RT. The progress of the reaction is followed by the consumption of sodium hydroxide solution. After the addition of 5.21 ml of sodium hydroxide solution, the reaction is stopped by addition of dichloromethane. The organic layer is separated, then washed three times with water, thereafter, dried over sodium sulfate, and finally evaporated. The crude ester is a slightly rose oil which after trituration in tert-butylmethylether at RT is obtained as a white solid. The product is collected on a filter funnel and yields after drying under high vacuum at RT 1.11 g (44.3% of theory) of (R)-1-(4-hydroxy-phenyl)-5-oxo-pyrrolidine-3-carboxylic acid methyl ester; m.p.: 122.9° C.; optical integrity: 97.9% e.e.; [α]20D=−35.2 (c=1.162 g/100 ml CHCl3).

Provenance & Evidence