Sodium Hydroxide → 4-{(S)-2-[4-(4-Chloro-benzyl)-phenoxymethyl]-pyrrolidin-1-yl}-butyric acid hydrochloride

Participants

Reaction Steps

To a solution of the product from step 3 (1.00 g, 2.49 mmol) in MeOH (10 mL) was added 2N NaOH (3.30 mL, 6.60 mmol). The resulting pink solution was stirred at ambient temperature overnight. The solvent was removed in vacuo. The crude oil was dissolved in water (20 mL) and the pH was adjusted to 7 with 2N HCl solution. The crude residue was extracted into ethyl acetate. The combined organic portions were washed with brine, dried over anhydrous Na2SO4, filtered and concentrated in vacuo. The crude product was purified by silica gel flash chromatography using MeOH/dichloromethane (gradient system) to give the free base of the title compound as a yellowish-brown oil. To the subsequent oil was added 2M HCl in diethyl ether (20 mL). The resulting mixture was stirred at ambient temperature for 6 hours. The solvents were decanted. The remaining off-white solid was triturated in diethyl ether (30 mL) overnight. The slurry was filtered, washed with diethyl ether (10 mL×3) and dried in vacuo at 45° C. overnight to afford the title compound as a white solid (0.61 g, 58%). 1H NMR (400 MHz, DMSO-d6); δ 1.72-2.02 (m, 5H), 2.22 (m, 1H), 2.37 (m, 2H), 3.13 (m, 2H), 3.46 (m, 1H), 3.61 (m, 1H), 3.85 (m, 1H), 3.88 (s, 2H), 4.27 (m, 2H), 6.92 (d, J=8.4 Hz, 2H), 7.17 (d, J=8.8 Hz, 2H), 7.22 (d, J=8.4 Hz, 2H), 7.33 (d, J=8.8 Hz, 2H), 10.47 (br s, 1H), 12.33 (br s, 1H); MS (m/z) 388.4 (M+1); LC (100.0%); HPLC (99.5%); Elemental Analysis (Calc) C, 62.27; H, 6.41; N, 3.30 (Found) C, 62.46; H, 6.47; N, 3.26.

Provenance & Evidence