Imidazole → 3-((tert-Butyldimethylsilyl)oxy)-4-fluoro-N-methoxy-N-methylbenzamide

HRID 1712840

반응식

HRID 1712840 반응식
[F:1][C:2]1[CH:13]=[CH:12][C:5]([C:6]([N:8]([O:10][CH3:11])[CH3:9])=[O:7])=[CH:4][C:3]=1[OH:14].N1C=CN=C1.[CH3:20][C:21]([Si:24](Cl)([CH3:26])[CH3:25])([CH3:23])[CH3:22]>CN(C=O)C>[Si:24]([O:14][C:3]1[CH:4]=[C:5]([CH:12]=[CH:13][C:2]=1[F:1])[C:6]([N:8]([O:10][CH3:11])[CH3:9])=[O:7])([C:21]([CH3:23])([CH3:22])[CH3:20])([CH3:26])[CH3:25]

참가 물질

5

반응물 3

HCID 795ImidazoleHCID 28928tert-Butyldimethylsilyl chlorideHCID 594590524-fluoro-3-hydroxy-N-methoxy-N-methylbenzamide

생성물 1

HCID 594586793-((tert-Butyldimethylsilyl)oxy)-4-fluoro-N-methoxy-N-methylbenzamide수율 67%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

To a solution of 4-fluoro-3-hydroxy-N-methoxy-N-methylbenzamide (1.90 g, 9.55 mmol) in DMF (8 mL) was added imidazole (740 mg, 10.8 mmol) and TBDMSCl (1.62 g, 10.8 mmol) at room temperature. The reaction mixture was stirred for 48 h and quenched with saturated NaHCO3. The solution was extracted with ether (3×) and the combined ether portions were washed with LiCl (10%), dried over Na2SO4, filtered and concentrated. The resulting colorless oil was purified by ISCO chromatography (120 g column) using hexanes/EtOAc (0-100% over 30 min) to give 3-(tert-butyldimethylsilyloxy)-4-fluoro-N-methoxy-N-methylbenzamide (RT=10-12 minutes) as a colorless oil (2.00 g, 67% yield). LCMS: RT=2.06 min [M+H] 314.22 (Phenomenex Luna C18 column, 4.6×30 mm eluting with 10-90% MeOH/H2O over 2 minutes containing 0.1% TFA; 5 mL/min, monitoring at 220 nm); NMR: 400 MHz 1H (CDCl3) 7.26 ppm, 2H, m; 7.02 ppm, 1H, m; 3.50 ppm, 3H, s; 3.31 ppm, 3H, s; 0.97 ppm, 9H, s, 0.16 ppm, 6H, s.

후처리

  1. customquenched with saturated NaHCO3
  2. extractionThe solution was extracted with ether (3×)
  3. washthe combined ether portions were washed with LiCl (10%)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe resulting colorless oil was purified by ISCO chromatography (120 g column)
  8. customhexanes/EtOAc (0-100% over 30 min)

출처 및 근거

ORD 기록
ord-bb88d2c8d7934d829600d189572d9833
출처 데이터셋
uspto-grants-2010_09
특허 번호
US07790770B2

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