1,4-Dioxane → 4-(3-Chloro-4-(trifluoromethyl)benzyloxy)-2,5-difluoro-N-(methylsulfonyl)benzamide

Participants

Reaction Conditions

Reaction Steps

To a solution of 1-bromo-4-(3-chloro-4-(trifluoromethyl)benzyloxy)-2,5-difluorobenzene (Preparation 19, 200 mg, 0.50 mmol) in 1,4-dioxane (2.0 mL) were added molybdenumhexacarbonyl (142 mg, 0.50 mmol), trans-bis(acetate)bis[(o-(di-o-tolylphosphino)benzyl]dipalladium (II) (23 mg, 0.025 mmol), tri-tertbutylphosphonium tetrafluoroborate (14 mg, 0.050 mmol), 1,8-diazobicylco[5.4.0]undec-7-ene (223 μL, 1.49 mmol) and methanesulphonamide (142 mg, 1.49 mmol). The reaction mixture was heated in the microwave at 140° C. for 20 minutes. The solvent was then evaporated in vacuo to yield a brown oil, which was dissolved in DCM (20 mL). Potassium hydrogen sulphate (30 mL) was added and the organic layer separated. The aqueous layer was extracted with DCM (2×20 mL), then the combined organics were washed with brine (50 mL), filtered through a phase separator and reduced to dryness to give a brown solid, which was purified by silica gel chromatography eluting with 2 to 10% methanol in DCM to yield the title compound as white solid (57 mg, 26%).

Provenance & Evidence