Reaktion #326057

Reaktionsgleichung

4-fluoro-3-hydroxy-N-methoxy-N-methylbenzamide

imidazole

TBDMSCl

→

3-(tert-butyldimethylsilyloxy)-4-fluoro-N-methoxy-N-methylbenzamide

Ausbeute 67.0%

Lösungsmittel

DMF

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigequenched with saturated NaHCO3
2. 2
   ExtraktionThe solution was extracted with ether (3×)
3. 3
   Waschenthe combined ether portions were washed with LiCl (10%)
4. 4
   Trocknendried over Na2SO4
5. 5
   Filtrationfiltered
6. 6
   Einengenconcentrated
7. 7
   SonstigeThe resulting colorless oil was purified by ISCO chromatography (120 g column)
8. 8
   Sonstigehexanes/EtOAc (0-100% over 30 min)

Vorschrift

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.

Quelle