Hydrochloric Acid → 4-(adamantan-1-ylmethoxy)-N-(azetidin-1-ylsulfonyl)-2-fluoro-5-iodobenzamide

Participants

Reaction Conditions

Reaction Steps

To a mixture of 4-(adamantan-1-ylmethoxy)-2-fluoro-5-iodobenzoic acid (1.75 g, 4.07 mmol) in anhydrous tetrahydrofuran (20 mL) was added 1,1′-carbonyldiimidazole (1.31 g, 8.10 mmol). The resulting mixture was heated at 70° C. for 30 minutes and then cooled to ambient temperature. Azetidine-1-sulfonamide (1.10 g, 8.10 mmol) was added followed by 1,8-diazabicyclo-[5.4.0]undec-7-ene (1.72 mL, 12.20 mmol) and the reaction mixture was stirred at ambient temperature for 16 hours. After addition of 1 N hydrochloric acid (5 mL) and diluting the mixture with ethyl acetate (150 mL), the organic phase was washed with 1 N hydrochloride acid (5 mL) and brine (10 mL); dried over anhydrous sodium sulfate. Filtration and concentration of the filtrate in vacuo gave a residue which was purified by silica gel column chromatography using 0-100% ethyl acetate in hexanes as eluent to afford the title compound as an off-white solid (0.48 g, 22%): 11H NMR (300 MHz, CDCl3) δ 8.51 (d, J=8.7 Hz, 1H), 6.56 (d, J=13.7 Hz, 1H), 3.90 (t, J=7.6 Hz, 4H), 3.59 (s, 2H), 2.35-2.15 (m, 2H), 2.12-1.99 (m, 3H), 1.83-1.63 (m, 12H); MS (ES−) m/z 547.1 (M−1).

Provenance & Evidence