反应详情

4.0 M Hydrogen chloride in dioxane (8.0 mL, 32 mmol) was added to a solution of tert-butyl 4-{[6-(hydroxymethyl)-2-(trifluoromethyl)pyrimidin-4-yl]amino}piperidine-1-carboxylate (0.58 g, 1.5 mmol, from Step 4) in 1,4-dioxane (3.9 mL) and the mixture was stirred until deprotection was complete as determined by LCMS. The mixture was then quenched by the addition of 1N NaOH to pH 12-13 (pH needs to be high enough for better extraction), and was saturated with solid NaCl. The product was extracted with 6 portions of chloroform, and the combined extracts were dried over sodium sulfate, filtered and concentrated to afford product as a white solid (0.43 g, 91%). 1H NMR (400 MHz, CDCl3) δ 6.48 (s, 1H), 4.65 (s, 2H), 3.13 (dt, J=11.9, 2.9 Hz, 2H), 2.81-2.66 (m, 2H), 2.04 (d, J=10.3 Hz, 2H), 1.51-1.31 (m, 2H). 19F NMR (376 MHz, CDCl3) δ −71.75 (s). LCMS (M+H): 277.1.

1. customThe mixture was then quenched by the addition of 1N NaOH to pH 12-13 (
2. extractionto be high enough for better extraction), and
3. extractionThe product was extracted with 6 portions of chloroform
4. dry with materialthe combined extracts were dried over sodium sulfate
5. filtrationfiltered
6. concentrationconcentrated