Water → 3-Methylbutanoic acid (1R)-1-[(benzyloxy)methyl]prop-2-en-1-yl ester

A solution of 19.9 ml of isobutyric acid chloride (163 mmol) in methylene chloride (20 ml) was added to a solution of 24.29 g of (2R)-1-(benzyloxy)but-3-en-2-ol obtained in Reference Example (1d) (136 mmol), 28.5 ml of triethylamine (205 mmol) and 1.65 g of N,N-dimethylaminopyridine (13.6 mmol) in methylene chloride (250 ml) under ice-cooling over 10 minutes, and the mixture was stirred at room temperature for four hours. 0.75 ml of water (42 mmol) was added to the reaction mixture, and the mixture was further stirred at room temperature for 15 minutes. The reaction mixture was concentrated under reduced pressure and diluted with 150 ml of water, followed by extraction with ethyl acetate. Then, the organic layer was washed with 1 M hydrochloric acid, a saturated sodium bicarbonate aqueous solution and brine and dried over anhydrous magnesium sulfate. After filtration, the solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (elution solvent:n-hexane/ethyl acetate=9/1) to obtain 34.96 g of the title compound (total yield over four steps: 95%).

1. temperaturecooling over 10 minutes
2. stirringthe mixture was further stirred at room temperature for 15 minutes
3. concentrationThe reaction mixture was concentrated under reduced pressure
4. additiondiluted with 150 ml of water
5. extractionfollowed by extraction with ethyl acetate
6. washThen, the organic layer was washed with 1 M hydrochloric acid
7. dry with materiala saturated sodium bicarbonate aqueous solution and brine and dried over anhydrous magnesium sulfate
8. filtrationAfter filtration
9. customthe solvent was evaporated under reduced pressure
10. customthe residue was purified by silica gel column chromatography (elution solvent:n-hexane/ethyl acetate=9/1)

ORD record

ord-81d15437ae3b46d5a679d0838d3eced3

Source dataset

uspto-grants-2012_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08158790B2