Reacción #607441

Ecuación de reacción

3′,5′-difluoroacetophenone

acetaldehyde

→

title compound

Rendimiento 40.0%

(−)-(S)-1-(3,5-difluorophenyl)ethanol

Rendimiento 40.0%

Disolventes

THF

Condiciones de reacción

Tratamiento posterior

1. 1
   Temperaturacooled to −27° C. to −25° C.
2. 2
   TemperaturaThe reaction was maintained at this temperature for 17 h
3. 3
   Otroto reach room temperature
4. 4
   OtroThe solvent was then removed in vacuo
5. 5
   Otrothe resulting residue was partitioned between water (10 mL) and TBME (tert-butyl-methyl ether) (20 mL)
6. 6
   ExtracciónThe aqueous phase was extracted again with TBME (20 mL)
7. 7
   LavadoThe organic layer was washed with an aqueous 2 N NaOH solution (20 mL), brine (20 mL)
8. 8
   Secadodried over anhydrous Na2SO4
9. 9
   Filtraciónfiltered
10. 10
    OtroThe solvent was removed in vacuo
11. 11
    Otroto give a residue, which
12. 12
    Otrowas purified by two subsequent column chromatographic steps

Procedimiento

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).

Fuente