반응 #607441

ord-0b8659006e4145b09ee1d587f3ff8831

반응 방정식

CC(=O)c1cc(F)cc(F)c1
3′,5′-difluoroacetophenone
CC=O
acetaldehyde
C[C@H](O)c1cc(F)cc(F)c1
title compound
수율 40.0%
C[C@H](O)c1cc(F)cc(F)c1
(−)-(S)-1-(3,5-difluorophenyl)ethanol
수율 40.0%

용매

반응 조건

상세 조건
See reaction.notes.procedure_details.

후처리

  1. 1
    온도cooled to −27° C. to −25° C.
  2. 2
    온도The reaction was maintained at this temperature for 17 h
  3. 3
    기타to reach room temperature
  4. 4
    기타The solvent was then removed in vacuo
  5. 5
    기타the resulting residue was partitioned between water (10 mL) and TBME (tert-butyl-methyl ether) (20 mL)
  6. 6
    추출The aqueous phase was extracted again with TBME (20 mL)
  7. 7
    세척The organic layer was washed with an aqueous 2 N NaOH solution (20 mL), brine (20 mL)
  8. 8
    건조dried over anhydrous Na2SO4
  9. 9
    여과filtered
  10. 10
    기타The solvent was removed in vacuo
  11. 11
    기타to give a residue, which
  12. 12
    기타was purified by two subsequent column chromatographic steps

실험 절차

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).

출처

DOI: 10.6084/m9.figshare.5104873.v1특허: US09326513B2uspto-grants-2016_05