Imidazole → (2RS,3RS)-2-(3,4-dichlorobenzyl)-3-(tert-butyldimethylsilyloxy)butanol

Temperature

-78 °C

1.14 g of tert-butyl (2RS, 3RS)-2-(3,4-dichlorobenzyl)-3-hydroxybutanoate obtained in Example 123 was dissolved in 10 ml of dimethylformamide, and 0.65 g of tert-butyldimethylchlorosilane and 0.37 g of imidazole were added thereto with stirring under cooling with ice. The mixture was stirred at room temperature for 6 hours. The reaction solution was diluted with ethyl ether, then washed with a saturated sodium hydrogencarbonate aqueous solution and a saturated sodium chloride aqueous solution, and dried over anhydrous magnesium sulfate. The drying agent was separated by filtration, and then the solvent was distilled off under reduced pressure. The residue was dissolved in 10 ml of toluene, and then a 1M toluene solution of diisobutylaluminum hydride was added thereto with stirring under cooling to -78° C. The mixture was stirred at the same temperature for 1 hour. A saturated ammonium chloride aqueous solution was added to the reaction solution with stirring under cooling to -78° C., and the temperature was raised to room temperature. Then, 1N hydrochloric acid and ethyl acetate were added thereto for liquid separation. The organic layer was washed with a saturated sodium chloride aqueous solution and then dried over anhydrous magnesium sulfate. The drying agent was separated by filtration, and then the solvent was distilled off under reduced pressure. The residue was subjected to silica gel column chromatography to obtain 0.99 g (yield: 76%) of (2RS, 3RS)-2-(3,4-dichlorobenzyl)-3-(tert-butyldimethylsilyloxy)butanol.

1. temperatureunder cooling with ice
2. stirringThe mixture was stirred at room temperature for 6 hours
3. washwashed with a saturated sodium hydrogencarbonate aqueous solution
4. dry with materiala saturated sodium chloride aqueous solution, and dried over anhydrous magnesium sulfate
5. customThe drying agent was separated by filtration
6. distillationthe solvent was distilled off under reduced pressure
7. dissolutionThe residue was dissolved in 10 ml of toluene
8. additiona 1M toluene solution of diisobutylaluminum hydride was added
9. stirringwith stirring
10. stirringThe mixture was stirred at the same temperature for 1 hour
11. additionA saturated ammonium chloride aqueous solution was added to the reaction solution
12. stirringwith stirring
13. temperatureunder cooling to -78° C.
14. temperaturethe temperature was raised to room temperature
15. additionThen, 1N hydrochloric acid and ethyl acetate were added
16. customfor liquid separation
17. washThe organic layer was washed with a saturated sodium chloride aqueous solution
18. dry with materialdried over anhydrous magnesium sulfate
19. customThe drying agent was separated by filtration
20. distillationthe solvent was distilled off under reduced pressure

ORD record

ord-4129b512324340dc89d3b9aee74bdf07

Source dataset

uspto-grants-1997_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05616803