Cesium carbonate → 5-(2,2-Difluoro-ethoxy)-7-chloro-2-(4-trifluoromethoxy-benzyl)-2,3-dihydro-isoindol-1-one

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Reaction Conditions

Reaction Steps

A mixture of 5-bromo-7-chloro-2-(4-trifluoromethoxy-benzyl)-2,3-dihydro-isoindol-1-one (0.126 g, 1 mmol), palladium(II) acetate (0.004 g, 0.02 mmol), rac-2-(di-t-butylphosphino)-1,1′-binaphthyl (0.009 g, 0.025 mmol), and cesium carbonate (0.163 g, 0.5 mmol) in toluene (5 mL) was treated with 2,2-difluoro ethanol (0.05 mL, 0.6 mmol) and stirred at 110° C. for 0.12 h. After this time the solvent was evaporated and silica gel column chromatography using, typically 30% ethyl acetate in hexane, afforded the desired product (0.06 g, 50%). 1H NMR (300 MHz, CDCl3): δ (ppm) 4.21 (m, 4H), 4.76 (s, 2H), 5.94-6.32 (m, 1H), 6.82 (s, 1H), 6.97 (s, 1H), 7.18 (d, 2H), 7.35 (d, 2H). GC-MS: m/z 421 (M)+.

Provenance & Evidence