反应 #607441

反应方程式

3′,5′-difluoroacetophenone

acetaldehyde

→

title compound

收率 40.0%

(−)-(S)-1-(3,5-difluorophenyl)ethanol

收率 40.0%

溶剂

THF

反应条件

后处理

1. 1
   温度cooled to −27° C. to −25° C.
2. 2
   温度The reaction was maintained at this temperature for 17 h
3. 3
   其他to reach room temperature
4. 4
   其他The solvent was then removed in vacuo
5. 5
   其他the resulting residue was partitioned between water (10 mL) and TBME (tert-butyl-methyl ether) (20 mL)
6. 6
   萃取The aqueous phase was extracted again with TBME (20 mL)
7. 7
   洗涤The organic layer was washed with an aqueous 2 N NaOH solution (20 mL), brine (20 mL)
8. 8
   干燥dried over anhydrous Na2SO4
9. 9
   过滤filtered
10. 10
    其他The solvent was removed in vacuo
11. 11
    其他to give a residue, which
12. 12
    其他was purified by two subsequent column chromatographic steps

实验过程

To a stirred solution of (−)-DIP-Cl ((−)-diisopinocampheylboron chloride) (2.67 g, 8.33 mmol, 1.3 eq) in THF (20 mL) kept under inert atmosphere (Ar) and cooled to −27° C. to −25° C., 3′,5′-difluoroacetophenone (1.00 g, 6.40 mmol) was added drop wise over 2 min. The reaction was maintained at this temperature for 17 h. The reaction mixture was then treated with acetaldehyde (0.44 mL, 7.69 mmol, 1.2 eq). Thereafter, the temperature was allowed to reach room temperature and the reaction mixture was stirred at for 7 h. The solvent was then removed in vacuo and the resulting residue was partitioned between water (10 mL) and TBME (tert-butyl-methyl ether) (20 mL). The aqueous phase was extracted again with TBME (20 mL). The organic layer was washed with an aqueous 2 N NaOH solution (20 mL), brine (20 mL), dried over anhydrous Na2SO4 and filtered. The solvent was removed in vacuo to give a residue, which was purified by two subsequent column chromatographic steps: First by normal phase chromatography (silica gel, heptane/ethyl acetate, v/v=1/0-9/1) followed by a reversed phase chromatography (90 C18-silica gel, acetonitrile for the second one). This gave the title compound (0.40 g, 40%) as a colorless oil with a specific rotation of [α]25D=−26.66 (c=1.054 g/100 mL, CH2Cl2, 589 nm).

来源