Hydrochloric Acid → 2-[2-(Piperidin-4-yloxy)-6-(trifluoromethyl)pyridin-4-yl]ethanol

Beteiligte Stoffe

Reaktionsschritte

2.5 M n-Butyllithium in hexanes (1.2 mL, 2.9 mmol) was added dropwise to a solution of tert-butyl 4-{[6-(trifluoromethyl)pyridin-2-yl]oxy}piperidine-1-carboxylate (0.50 g, 1.4 mmol, from Step 1) in tetrahydrofuran (8.0 mL) at −78° C. The reaction was stirred at this temperature for 1.5 hours, and 1,3,2-dioxathiolane 2,2-dioxide (0.36 g, 2.9 mmol, Aldrich) in Tetrahydrofuran (2.0 mL) was added. The mixture was allowed to warm to room temperature and stir overnight. 12 N Hydrogen chloride in water (0.72 mL, 8.7 mmol) was added to the mixture. The mixture was stirred at room temperature for 4 hours. The mixture was then treated with saturated sodium bicarbonate to pH between 7 and 8, and brine was added. The mixture was then extracted with DCM four times. The combined extracts were dried over sodium sulfate, filtered and concentrated. Preparative HPLC-MS (C18 eluting with a gradient of MeCN/H2O containing 0.15% NH4OH) was used to purify the product. It was the second peak to elute having the desired mass. 1H NMR (300 MHz, CD3OD) δ 7.24 (s, 1H), 6.86 (s, 1H), 5.16 (tt, J=8.4, 3.9 Hz, 1H), 3.80 (t, J=6.3 Hz, 2H), 3.06 (dt, J=12.6, 4.6 Hz, 2H), 2.85 (t, J=6.3 Hz, 2H), 2.73 (ddd, J=12.7, 9.5, 3.2 Hz, 2H), 2.13-1.93 (m, 2H), 1.68 (dtd, J=13.0, 9.1, 3.9 Hz, 2H). 19F NMR (282 MHz, CD3OD) δ −70.29 (s). LCMS (M+H)+: 291.1

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