反応 #607441

ord-0b8659006e4145b09ee1d587f3ff8831

反応方程式

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

溶媒

反応条件

詳細条件
See reaction.notes.procedure_details.

後処理

  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
    その他to reach room temperature
  4. 4
    その他The solvent was then removed in vacuo
  5. 5
    その他the resulting residue was partitioned between water (10 mL) and TBME (tert-butyl-methyl ether) (20 mL)
  6. 6
    抽出The aqueous phase was extracted again with TBME (20 mL)
  7. 7
    洗浄The organic layer was washed with an aqueous 2 N NaOH solution (20 mL), brine (20 mL)
  8. 8
    乾燥dried over anhydrous Na2SO4
  9. 9
    ろ過filtered
  10. 10
    その他The solvent was removed in vacuo
  11. 11
    その他to give a residue, which
  12. 12
    その他was purified by two subsequent column chromatographic steps

実験手順

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).

出典

DOI: 10.6084/m9.figshare.5104873.v1特許: US09326513B2uspto-grants-2016_05