Imidazole → 2-(Tert-butyldimethylsilyloxy)-5-(2,3-difluorophenyl)cycloheptanol

HRID 1099157노트

반응식

HRID 1099157 반응식
[F:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[CH:4][C:3]=1[CH:9]1[CH2:15][CH2:14][CH:13]([OH:16])[CH:12]([OH:17])[CH2:11][CH2:10]1.[Si:18](Cl)([C:21]([CH3:24])([CH3:23])[CH3:22])([CH3:20])[CH3:19].N1C=CN=C1.CCCCCC.CCOC(C)=O>CN(C=O)C.O>[Si:18]([O:17][CH:12]1[CH2:11][CH2:10][CH:9]([C:3]2[CH:4]=[CH:5][CH:6]=[C:7]([F:8])[C:2]=2[F:1])[CH2:15][CH2:14][CH:13]1[OH:16])([C:21]([CH3:24])([CH3:23])[CH3:22])([CH3:20])[CH3:19]

참가 물질

7

반응물 4

HCID 795ImidazoleHCID 28928tert-Butyldimethylsilyl chlorideHCID 21226206Ethyl acetate hexaneHCID 579114025-(2,3-Difluorophenyl)cycloheptane-1,2-diol

생성물 1

HCID 579114932-(Tert-butyldimethylsilyloxy)-5-(2,3-difluorophenyl)cycloheptanol

시약·촉매·용매 2

HCID 962Water용매HCID 6228Dimethylformamide용매

실험 절차

In a 250 mL round-bottomed flask (t=g) was added 5-(2,3-difluorophenyl)cycloheptane-1,2-diol (1.454 g, 6.0 mmol) (crude material, azeotroped with dry benzene) in DMF (20 mL) to give a colorless solution. TBS-Cl (0.995 g, 6.60 mmol) and imidazole (0.980 g, 14.40 mmol) were added, and the mixture was stirred at room temperature for 5 hours. TLC (2/1 hexane/EtOAc) indicated complete conversion to two main spots. It was diluted with water and extracted with EtOAc twice. The combined organic layers were washed with brine, dried with Na2SO4 and concentrated to a colorless oil. Purification by FCC up to 30% EtOAc/hexane afforded the desired mono-protected product as a broad peak. The product fractions were pooled and concentrated to a colorless oil (1.79 g, 84% for two steps). 1H NMR (400 MHz, CDCl3) δ 7.02-6.85 (m, 3H), 3.98-3.70 (m, 2H), 3.18-3.02 (m, 1H), 2.15-1.82 (m, 4H), 1.80-1.45 (m, 4H), 0.91 (s, 9H), 0.90 (2 s, 6H).

후처리

  1. customto give a colorless solution
  2. extractionextracted with EtOAc twice
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried with Na2SO4
  5. concentrationconcentrated to a colorless oil
  6. customPurification by FCC up to 30% EtOAc/hexane
  7. customafforded the desired mono-protected product as a broad peak
  8. concentrationconcentrated to a colorless oil (1.79 g, 84% for two steps)

출처 및 근거

ORD 기록
ord-57c354c4f80143a5a9d7978ef5dae57d
출처 데이터셋
uspto-grants-2012_03
특허 번호
US08143403B2

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