Sodium Hydroxide → (+/-)-4-(1-((3-Methylquinolin-2-yl)amino)butyl)benzoic acid

Participants

Reaction Steps

To a solution of Intermediate 4 (34.29 g, 94.60 mmol) in tetrahydrofuran (234 mL) and methanol (234 mL) was added 1 N aq sodium hydroxide (473 mL). The solution was stirred at room temperature for 16 h. The solution was concentrated under reduced pressure to remove tetrahydrofuran and methanol. 3 N aqueous hydrochloric acid was added dropwise to pH 2. The resulting slurry was filtered, and the solid was washed with water (300 mL, then 100 mL). The solid was dried by azeotropic removal of water first with toluene, then heptane (7×100 mL), followed by heating to 70° C. under reduced pressure to afford (+/−)-4-(1-((3-methylquinolin-2-yl)amino)butyl)benzoic acid (Intermediate 5). 1H NMR (400 MHz, CD3OD) δ 8.09 (s, 1 H), 8.02 (d, J=8.4 Hz, 2 H), 7.84 (d, J=8.4 Hz, 1 H), 7.72 (d, J=7.8 Hz, 1 H), 7.66-7.58 (m, 3 H), 7.40 (t, J=7.6 Hz, 1 H), 5.56 (dd, J=6.0, 8.6 Hz, 1 H), 2.49 (s, 3 H), 2.24-2.10 (m, 1 H), 2.08-1.95 (m, 1 H), 1.66-1.52 (m, 1 H), 1.52-1.39 (m, 1 H), 1.03 (t, J=7.4 Hz, 3 H).

Provenance & Evidence