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

HRID 1874297Notes

Reaction equation

HRID 1874297 reaction equation
[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]

Participants

5

Reactant 3

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

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.

Workup

  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)

Sources & evidence

ORD record
ord-ce76f022051446e491fda92ca36038df
Source dataset
uspto-grants-2012_11
Patent number
US08304403B2

Reaction notes

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