Hydrochloric Acid → 4-((adamantan-2-yloxy)methyl)-5-cyclopropyl-2-fluoro-N-(methylsulfonyl)benzamide

Participants

Reaction Conditions

Reaction Steps

To a solution of 4-((adamantan-2-yloxy)methyl)-5-chloro-2-fluoro-N-(methylsulfonyl)-benzamide (0.30 g, 0.72 mmol), cyclopropylboronic acid (0.40 g, 4.65 mmol) and potassium phosphate (2.55 g, 12.00 mmol) in toluene (10 mL) and water (0.5 mL) was bubbled with a nitrogen atmosphere for 10 min, tricyclohexylphosphine tetrafluoroborate (0.17 g, 0.48 mmol) and palladium acetate (0.05 g, 0.22 mmol) was added to this reaction mixture. The reaction mixture was heated to 100° C. for 18 h under a nitrogen atmosphere and then cooled to ambient temperature. 5% aqueous hydrochloric acid (20 mL) was added and the mixture was extracted with ethyl acetate (100 mL×3), the combined organics were 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 (0.19 g, 62%): 1H NMR (300 MHz, CDCl3) δ 8.81 (br s, 1H), 7.69 (d, J=7.8 Hz, 1H), 7.40 (d, J=13.5 Hz, 1H), 4.71 (s, 2H), 3.60 (br s, 1H), 3.41 (s, 3H), 2.16-2.03 (m, 4H), 1.90-1.51 (m, 11H), 0.97-0.90 (m, 2H), 0.68-0.62 (m, 2H); MS (ES−) m/z: 420.35 (M−1).

Provenance & Evidence