Methanol → 2-(3,5-difluorophenyl)-2-methoxyacetic acid

HRID 1071441노트

반응식

HRID 1071441 반응식
[F:1][C:2]1[CH:3]=[C:4]([CH:7]=[C:8]([F:10])[CH:9]=1)[CH:5]=[O:6].[CH:11](Br)(Br)Br.[OH-:15].[K+].[CH3:17][OH:18]>O.[Cl-].[Na+].O>[F:1][C:2]1[CH:3]=[C:4]([CH:5]([O:6][CH3:11])[C:17]([OH:18])=[O:15])[CH:7]=[C:8]([F:10])[CH:9]=1

참가 물질

7

반응물 4

HCID 887MethanolHCID 5558BromoformHCID 14797Potassium HydroxideHCID 5881603,5-Difluorobenzaldehyde

생성물 1

HCID 223929272-(3,5-difluorophenyl)-2-methoxyacetic acid

시약·촉매·용매 2

HCID 962Water용매HCID 57417360Sodium chloride; water용매

실험 절차

The title compound was prepared according to the general procedure in Reeve, et al, J.A.C.S., 83:2755 (1961). A solution of 3,5-difluorobenzaldehyde (Aldrich) and bromoform (1.2 eq.) In methanol was cooled to −5° C. and treated dropwise with methanolic KOH. The reaction temperature was held below 6 C. during the addition. The mixture was slowly warmed to room temperature and stirred overnight. The suspension was diluted with water and 50% saturated aqueous brine. The mixture was extracted with ether, and the aqueous layer was acidified to a pH around 3.5 and extracted with ether. The latter organic phase was dried over sodium sulfate, filtered and concentrated. The crude acid was purified via flash chromatography eluting with 1:4:95 acetic acid/methanol/methylene chloride to give a white solid. 1H NMR (300 MHz. CDCl3) δ 11.36 (1H, bs), 7.05 (1H, m), 6.81 (2H, tt, J=2.4, 8.8 Hz), 4.77 (1H, s), 3.47 (3H, s)/C9H8F2O3 (MW=202.17); mass spectroscopy—202.

후처리

  1. additionduring the addition
  2. extractionThe mixture was extracted with ether
  3. extractionextracted with ether
  4. dry with materialThe latter organic phase was dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude acid was purified via flash chromatography
  8. washeluting with 1:4:95 acetic acid/methanol/methylene chloride
  9. customto give a white solid

출처 및 근거

ORD 기록
ord-288de7d8cb674814a79cdd328cf1ca4b
출처 데이터셋
uspto-grants-2005_06
특허 번호
US06906056B2

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