反应详情

To a solution of tert-butyl 4-{[(3,4-dioxo-3,4-dihydronaphthalen-1-yl)thio]methyl}-4-hydroxypiperidine-1-carboxylate (3.8 g, 0.942 mmol) in 50 ml dichloromethane which was cooled to 0° C. was added trifluoroacetic acid (200 ml). The reaction mixture was stirred at room temperature for 30 hours and the solvent removed under reduced pressure. The mixture was dissolved in dichloromethane (150 ml) and poured over a 0° C. mixture of saturated sodium carbonate (500 ml) and water (200 ml). Methanol (500 ml) was then added to the reaction mixture and allowed to stir overnight. The mixture was extracted with dichloromethane (4×400 ml). The organic extracts were combined and washed with a mixture of 2.0M sodium carbonate and brine (5×500 ml). The organic layer was separated, dried with Na2SO4, and concentrated under reduced pressure to give a purple solid. To a stirred solution of the purple solid in dichloromethane (100 ml), 4.0 M HCl in dioxane (20 ml) was added dropwise. The precipitate was filtered, washed with dichloromethane and ether, and recrystallized from ethanol to give a purple crystalline solid (1.84 g, 58%). M.p.=229-232° C.; 400 MHz 1H NMR (DMSO-d6) δ: 9.19 (br. s, 2H), 7.90-7.86 (m, 1H), 7.84-7.80 (m, 1H), 7.76-7.71 (m, 1H), 7.58-7.53 (m, 1H), 3.33-3.25 (m, 2H), 3.16-3.07 (m, 4H), 2.22-2.15 (m, 2H), 2.20-1.50 (m, 2H); LCMS: 302 [M+H].

1. customthe solvent removed under reduced pressure
2. dissolutionThe mixture was dissolved in dichloromethane (150 ml)
3. additionpoured over a 0° C.
4. additionmixture of saturated sodium carbonate (500 ml) and water (200 ml)
5. additionMethanol (500 ml) was then added to the reaction mixture
6. stirringto stir overnight
7. extractionThe mixture was extracted with dichloromethane (4×400 ml)
8. washwashed with a mixture of 2.0M sodium carbonate and brine (5×500 ml)
9. customThe organic layer was separated
10. dry with materialdried with Na2SO4
11. concentrationconcentrated under reduced pressure
12. customto give a purple solid
13. filtrationThe precipitate was filtered
14. washwashed with dichloromethane and ether
15. customrecrystallized from ethanol