Tetrahydrofuran → Amg 333

Participants

Reaction Steps

To a solution of (S)-methyl 6-(((3-fluoro-4-(trifluoromethoxy)phenyl)(3-fluoropyridin-2-yl)methyl)carbamoyl)nicotinate (11.5 g, 24.61 mmol) in MeOH (140 mL, Aldrich) was added lithium hydroxide hydrate (2.065 g, 49.2 mmol, Aldrich). The mixture was stirred at room temperature for 5 min followed by the addition of THF (5 mL, Aldrich) and the mixture was stirred at room temperature for 1 h. The mixture was concentrated in vacuo, cooled to 0° C. and was adjusted to pH=6-7 with concentrated HCl. EtOAc (300 mL) was added to the adjusted pH mixture, and the resulting mixture was stirred at room temperature for 15 min. The organic layer was collected and the aqueous phase was extracted with EtOAc (1×200 mL). The combined organic layers were dried over MgSO4 and concentrated in vacuo. The residue was then dissolved in MeOH (400 mL) and silica gel was added. The mixture was concentrated and dried in vacuo. The solid mixture was then purified by silica gel flash column chromatography using ISCO instrument (solid loading, 40% EtOAc/hexane, then 10% MeOH in EtOAc) to give the title compound as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 13.75 (br. s., 1H), 9.85 (d, J=7.4 Hz, 1H), 9.18 (d, J=1.4 Hz, 1H), 8.58 (d, J=4.7 Hz, 1H), 8.48 (dd, J=8.1, 2.1 Hz, 1H), 8.16 (d, J=8.0 Hz, 1H), 7.83 (t, J=9.3 Hz, 1H), 7.50-7.61 (m, 3H), 7.36 (d, J=8.4 Hz, 1H), 6.58 (d, J=7.2 Hz, 1H). MS (ESI, positive ion) m/z: 454.0 (M+H)

Provenance & Evidence