Hexane → (S)-4-Benzyl-3-[(2R,4E)-6-benzyloxy-2-propylhex-4-enoyl]oxazolidin-2-one

Temperature

-40 °C

165 ml of a solution of sodium bis(trimethylsilyl)amide in n-hexane (1.03 mol/l) (169 mmol) was added to a solution of 37.0 g of (S)-4-benzyl-3-pentanoyloxazolidin-2-one obtained in Reference Example 6 (142 mmol) in tetrahydrofuran (330 ml) under a nitrogen atmosphere and at −78° C. over 45 minutes, and the mixture was stirred at the same temperature for 30 minutes. Then, a solution of 35.8 g of [(E)-4-bromobut-2-enyloxymethyl]benzene obtained in Reference Example 4 (148 mmol) in tetrahydrofuran (80 ml) was added to the solution obtained above over 30 minutes, and the mixture was stirred at the same temperature for 30 minutes. Thereafter, the mixture was raised to −40° C. and further stirred for four hours. 90 ml of an ammonium chloride aqueous solution was added to the reaction mixture, and the mixture was further stirred at room temperature for one hour. The reaction mixture was concentrated under reduced pressure and diluted with 500 ml of water, followed by extraction with ethyl acetate. Then, the organic layer was washed with water 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=7/1-2/1) to obtain 47.3 g of the title compound (yield: 79%).

1. additionwas added to the solution
2. customobtained above over 30 minutes
3. stirringthe mixture was stirred at the same temperature for 30 minutes
4. stirringfurther stirred for four hours
5. stirringthe mixture was further stirred at room temperature for one hour
6. concentrationThe reaction mixture was concentrated under reduced pressure
7. additiondiluted with 500 ml of water
8. extractionfollowed by extraction with ethyl acetate
9. washThen, the organic layer was washed with water and brine
10. dry with materialdried over anhydrous magnesium sulfate
11. filtrationAfter filtration
12. customthe solvent was evaporated under reduced pressure
13. customthe residue was purified by silica gel column chromatography (elution solvent:n-hexane/ethyl acetate=7/1-2/1)

ORD record

ord-bad0baa4a1a84c07b1d3cf49fd9c969b

Source dataset

uspto-grants-2012_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08158790B2