Реакция #607441

Уравнение реакции

3′,5′-difluoroacetophenone

acetaldehyde

→

title compound

Выход 40.0%

(−)-(S)-1-(3,5-difluorophenyl)ethanol

Выход 40.0%

Растворители

THF

Условия реакции

Обработка

1. 1
   Температураcooled to −27° C. to −25° C.
2. 2
   ТемператураThe reaction was maintained at this temperature for 17 h
3. 3
   Другоеto reach room temperature
4. 4
   ДругоеThe solvent was then removed in vacuo
5. 5
   Другоеthe resulting residue was partitioned between water (10 mL) and TBME (tert-butyl-methyl ether) (20 mL)
6. 6
   ЭкстракцияThe aqueous phase was extracted again with TBME (20 mL)
7. 7
   ПромывкаThe organic layer was washed with an aqueous 2 N NaOH solution (20 mL), brine (20 mL)
8. 8
   Сушкаdried over anhydrous Na2SO4
9. 9
   Фильтрацияfiltered
10. 10
    ДругоеThe solvent was removed in vacuo
11. 11
    Другоеto give a residue, which
12. 12
    Другоеwas purified by two subsequent column chromatographic steps

Методика

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).

Источник