Water → Ethyl 7-hydroxychromane-2-carboxylate

This ester was then resubmitted to enzymatic hydrolysis with Pseudomonas lipase (P-30, Amano International) to enhance its enantiomeric purity. A 3 L three-necked flask equipped as described above was charged with 775 mL of deionized water, 194 mL of 0.05M phosphate buffer (pH 7.0) and 28.4 g (0.128 mol) of the above ester in 96 mL of tetrahydrofuran. The pH was adjusted to 8 with adequate 1.0N aqueous sodium hydroxide solution and 2.6 g of Pseudomonas lipase enzyme (P-30 Amano) was added to the mixture. The hydrolysis was allowed to proceed to 70% conversion over a 7 hour period while stirring at a fast rate and maintaining the pH at 8. The tetrahydrofuran was removed from the reaction mixture at 40° C. (10 mm Hg) and the aqueous phase was extracted with 3×250 mL=750 mL of ethyl acetate. The combined organic layers were washed successively with 250 mL of saturated aqueous sodium bicarbonate solution and 250 mL of deionized water. The organic phase was dried over anhydrous sodium sulfate, filtered and concentrated at 40° C. (10 mm Hg) to give 6.7 g of nearly racemic 3,4-dihydro-7-hydroxy-2H-benzopyran-2-carboxylic acid ethyl ester. The aqueous layers were acidified to pH=1 with 33 mL of concentrated hydrochloric acid and extracted with 3×250 mL=750 mL of ethyl acetate. The combined organic layers were washed with 250 mL of brine and dried over anhydrous sodium sulfate. After filtration, the solvent was removed at 40° C. (10 mm Hg) to give 20.4 g of (S)-3,4-dihydro-7-hydroxy-2H-1-benzopyran-2-carboxylic acid, 95.5% e.e. This material was esterified as described above to give 21.6 g (76% yield) of (S)-3,4-dihydro-7-hydroxy-2H-1-benzopyran-2-carboxylic acid, ethyl ester as a beige solid, m.p. 77°-79° C.; (α)D22 +19.1° C. (c 1.0, CHCl3); 95.5% e.e.

1. customA 3 L three-necked flask equipped
2. additionwas added to the mixture
3. temperaturemaintaining the pH at 8
4. customThe tetrahydrofuran was removed from the reaction mixture at 40° C. (10 mm Hg)
5. extractionthe aqueous phase was extracted with 3×250 mL=750 mL of ethyl acetate
6. washThe combined organic layers were washed successively with 250 mL of saturated aqueous sodium bicarbonate solution and 250 mL of deionized water
7. dry with materialThe organic phase was dried over anhydrous sodium sulfate
8. filtrationfiltered
9. concentrationconcentrated at 40° C. (10 mm Hg)

ORD record

ord-fc72ac0c2cb74ea2b18423b7f9159ad1

Source dataset

uspto-grants-1991_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05037747