Triethylamine → 4-((adamantan-1-yloxy)methyl)-5-chloro-2-fluoro-N-(methylsulfonyl)benzamide

Participants

Reaction Conditions

Reaction Steps

A mixture of 1-((4-bromo-2-chloro-5-fluorobenzyl)oxy)adamantane (0.37 g, 1.00 mmol), methanesulfonamide (0.29 g, 3.00 mmol), molybdenumhexacarbonyl (0.27 g, 1.00 mmol) and triethylamine (0.6 mL, 4.30 mmol) in dioxane was purged with nitrogen for 5 min, xantphos (0.10 g, 0.18 mmol) and palladium acetate (0.02 g, 2.00 mmol) were added to the reaction mixture. The reaction mixture was heated at 100° C. for 1 h under microwave irradiation (300 psi) and then cooled to ambient temperature, diluted with methylene chloride (100 mL) and saturated ammonium chloride (20 mL). The organic layer was washed with brine; dried over anhydrous sodium sulfate and concentrated in vacuo. Purification of the residue by column chromatography (10% to 30% gradient ethyl acetate in hexanes) afforded the title compound as a colorless solid (0.12 g, 28%): 1H NMR (300 MHz, CDCl3) δ 8.74 (br s, 1H), 8.01 (d, J=6.9 Hz, 1H), 7.49 (d, J=12.9 Hz, 1H), 4.57 (s, 2H), 3.41 (s, 3H), 2.18 (br s, 3H), 1.84-1.81 (m, 6H), 1.70-1.54 (m, 6H); MS (ES−) m/z: 414.1, 416.1 (M−1).

Provenance & Evidence