Hydrochloric Acid → 4-(Adamantan-1-ylmethoxy)-5-bromo-2-fluorobenzoic acid

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Reaction Steps

A mixture of adamantan-1-ylmethanol (3.51 g, 21.10 mmol) and potassium tert-butoxide (5.45 g, 48.5 mmol) in anhydrous dimethylsulfoxide (125 mL) was stirred for 20 minutes. To the reaction mixture was then added 5-bromo-2,4-difluorobenzoic acid (5.00 g, 21.10 mmol) followed by anhydrous dimethylsulfoxide (25 mL). The resulting mixture was stirred for 18 hours at ambient temperature. The reaction mixture was diluted with water (300 mL), and adjusted to pH 3 with 3 M hydrochloric acid. The obtained solid was filtered off and rinsed with water (200 mL) to provide a 2:1 mixture of the title compound and 2-adamantan-1-ylmethoxy)-5-bromo-4-fluorobenzoic acid (6.97 g, 86%). Major isomer: 1H NMR (300 MHz, DMSO-d6) δ 7.94 (d, J=7.9 Hz, 1H), 7.05 (d, J=12.9 Hz, 1H), 3.65 (s, 2H), 1.98-1.83 (m, 3H), 1.72-1.48 (m, 12H); MS (ES−) m/z 381.13, 383.12 (M−1).

Provenance & Evidence