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

HRID 1712840

Reaktionsgleichung

Reaktionsgleichung von HRID 1712840
[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]

Komponenten

5

Edukt 3

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

Produkt 1

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

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

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.

Aufarbeitung

  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)

Quellen und Nachweise

ORD-Eintrag
ord-bb88d2c8d7934d829600d189572d9833
Quelldatensatz
uspto-grants-2010_09
Patentnummer
US07790770B2

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