Water → HCID 54007512, compound

Participants

Reaction Steps

A 5 L three-necked flask equipped with a mechanical stirrer, a pH electrode connected to a pH control unit and an addition tube connected to a peristaltic pump, was charged with 2.73 L of deionized water, 682 mL of 0.05M phosphate buffer (pH 7.0) and a solution of 100.0 g (0.45 mol) of racemic-3,4-dihydro-7-hydroxy-2H-1-benzopyran-2-carboxylic acid ethyl ester in 340 mL of tetrahydrofuran. The pH was adjusted to 8 with adequate 1.0N aqueous sodium hydroxide solution, and 9.0 g of Pseudomonas lipase enzyme (P-30, Amano International) was added to the mixture. The hydrolysis was allowed to proceed while stirring at a fast rate and keeping the pH at 8 by adding adequate 1.0N aqueous sodium hydroxide solution via the pump. The hydrolysis was stopped when 40% of the base has been consumed. The tetrahydrofuran in the reaction mixture was removed at 40° C. (10 mm Hg of vacuum) and the aqueous phase was extracted 3×1.0 L=3.0 L of ethyl acetate. The combined organic extracts were washed successively with 500 mL of saturated aqueous sodium bicarbonate solution and 500 mL of brine, then dried over anhydrous sodium sulfate. The drying agent was removed by filtration and the solvent was removed at 35° C. (10 mm Hg) to give 35.1 g (35% yield; 86% of theory) of (R)-3,4-dihydro-7-hydroxy-2H-1-benzopyran-2-carboxylic acid, ethyl ester as a beige solid, m.p. 77°-78° C.; (α)D22 -18.8° (c 1.0, CHCl3); 93.5% e.e.

Provenance & Evidence