Reaktion #326058

Reaktionsgleichung

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

HCl

1-bromo-3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)benzene

nBuLi

→

(3-(tert-butyldimethylsilyloxy)-4-fluorophenyl)(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)methanone

Ausbeute 71.0%

Lösungsmittel

ether

ether

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.STIRRINGthe reaction mixture was stirred at −78° C. for 1.5 h
2. 2
   Waschento rinse the reaction flask
3. 3
   SonstigeThe aqueous phase was separated
4. 4
   Extraktionextracted with diethyl ether (20 mL)
5. 5
   TrocknenThe combined ether portions were dried over Na2SO4
6. 6
   Filtrationfiltered
7. 7
   Einengenconcentrated
8. 8
   SonstigeThe resulting oil was purified by ISCO chromatography (120 g column)
9. 9
   Sonstigehexanes/EtOAc (0-100% over 30 min)

Vorschrift

At −78° C. under argon, to a solution of 1-bromo-3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)benzene (2.04 g, 7.01 mmol) in anhydrous ether (20 mL) was added nBuLi (3.5 mL, 2.0 M in cyclohexane, 7.0 mmol) dropwise and the reaction mixture was stirred for 1 h. 3-(Tert-butyldimethylsilyloxy)-4-fluoro-N-methoxy-N-methylbenzamide (2.00 g, 6.38 mmol) was added in one portion and the reaction mixture was stirred at −78° C. for 1.5 h. The pale yellow solution was poured into a 1 N HCl aqueous solution (30 mL) and ether (30 mL) was used to rinse the reaction flask. The aqueous phase was separated and extracted with diethyl ether (20 mL). The combined ether portions were dried over Na2SO4, filtered and concentrated. The resulting oil was purified by ISCO chromatography (120 g column) using hexanes/EtOAc (0-100% over 30 min) to give (3-(tert-butyldimethylsilyloxy)-4-fluorophenyl)(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)methanone at a retention time of 7 min (2.11 g, 71% yield). LCMS: RT=2.41 min [M+H] 465.19 (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) 7.33 ppm, 3H, m; 7.28 ppm, 1H, m; 7.11 ppm, 2H, m; 5.86 ppm, 1H, t, J=53.39 Hz; 0.95 ppm, 9H, s; 0.15 ppm, 6H, s.

Quelle