Acetic Acid → GW3965 hydrochloride

Participants

Reaction Steps

A solution of methyl (3-{3-[[2-chloro-3-(trifluoromethyl)benzyl](2,2-diphenylethyl)amino]propoxy}phenyl)acetate (113 mg, 0.19 mmol) in 1.5 mL of tetrahydrofuran and 1 mL of water was treated with 1N aqueous LiOH (0.29 mL, 0.29 mmol). After stirring at room temperature for 2 hours, additional 1N aqueous LiOH (0.29 mL, 0.29 mmol) was added and stirring was continued for 2 hours. The reaction was neutralized with AcOH (66 μL, 0.58 mmol) and poured into H2O/EtOAc. The layers were separated and the aqueous layer was extracted with EtOAc (3×). The combined organic layers were washed with brine (1×), dried over magnesium sulfate, filtered, and concentrated in vacuo. The crude material was purified by preparative thin layer chromatography (silica gel, 1 mm plates, Merck 20×20 cm silica gel 60 F254) eluting with CH2Cl2:MeOH (95:5) to afford an oil. The oil was dissolved in Et2O and acidified with excess HCl/Et2O. The reaction was concentrated in vacuo and dried under reduced pressure to give 65 mg (56% yield) of the title compound as a white solid: H NMR (C5D5N, 400 MHz) δ 7.60–7.05 (m, 15 H), 7.01 (t, 1 H, J=7.6), 6.84 (dd, 1 H, J=8.4, 2.4), 4.32 (t, 1 H, J=7.6), 3.89 (s, 2 H), 3.77 (s, 2 H), 3.71 (t, 2 H, J=5.6), 3.16 (d, 2 H, J=7.6), 2.65 (t, 2 H, J=6.4), 1.88–1.78 (m, 2 H).

Provenance & Evidence