反应详情

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

1. stirringstir overnight
2. stirringThe mixture was stirred at room temperature for 4 hours
3. additionwas added
4. extractionThe mixture was then extracted with DCM four times
5. dry with materialThe combined extracts were dried over sodium sulfate
6. filtrationfiltered
7. concentrationconcentrated
8. washPreparative HPLC-MS (C18 eluting with a gradient of MeCN/H2O containing 0.15% NH4OH)
9. customto purify the product
10. washto elute