Ammonia → HCID 58993548, compound

Participants

Reaction Conditions

Reaction Steps

3-Bromo-5-(((1-(tert-butoxycarbonyl)-4-phenylpiperidin-4-yl)methoxy)methyl)benzoic acid (0.66 g, 1.31 mmol), 4-fluorophenylboronic acid (0.55 g, 3.93 mmol), and tetrakis(triphenylphosphine) palladium(0) (82 mg, 0.05 mmol) were combined in dry tetrahydrofuran (10 mL) in a microwave tube and sealed. After flushing with nitrogen, 5.5 mL of a 1 N potassium hydroxide aqueous solution was introduced. The mixture was heated at 120° C. for 1 h via microwave. After cooling to room temperature, the reaction mixture was concentrated, dissolved in dimethylformamide (6 mL) and cooled to 0° C. The reaction mixture was sequentially treated with methylene chloride (2 mL), 7 N ammonia in methanol (0.33 mL, 2.3 mmol), N,N-diisopropylethylamine (0.51 mL, 2.9 mmol), and PyBop® (0.72 g, 1.4 mmol). The ice bath was removed and the solution stirred for 1.5 h and concentrated. The product was purified by column chromatography (50% ethyl acetate/hexanes) to give 0.4 g (66%). 1H-NMR (CDCl3, 500 MHz) δ 7.85 (s, 1H), 7.43-7.46 (m, 2H), 7.41 (s, 1H), 7.37 (s, 1H), 7.28-7.31 (m, 4H), 7.15-7.18 9 (m, 1H), 7.07-7.10 (m, 2H), 4.40 (s, 2H), 3.67-3.69 (m, 2H), 3.40 (s, 2H), 2.96-3.00 (m, 2H), 2.14-2.16 (m, 2H), 1.80-1.86 (m, 2H), 1.37 (s, 9H). Mass spec.: 519.39 (MH)+.

Provenance & Evidence