反应详情

To OXONE® (155 g, 253 mmol) in H2O (425 mL) and EtOH (250 mL) at 0° C. was added 1-[2-methyl-5-(methyloxy)-4-nitrophenyl]-4-[2-(methylthio)ethyl]piperidine (32.8 g, 101 mmol) in EtOAc (250 mL) via addition funnel over the period of an hour. The reaction was warmed to rt and allowed to stir for 30 min at which time it was determined to be complete by LCMS. The reaction was diluted with H2O and EtOAc. The resultant precipitate was filtered and washed with EtOAc. The layers of the filtrate were separated and the aqueous layer was washed with EtOAc (3×). The filtered solids were dissolved with DCM and H2O and the layers were separated. The organic layer was washed with DCM (2×). The combined organic layer was dried (MgSO4), filtered, and rotovapped down. The resultant solid was triturated with diethyl ether, filtered, and dried under vacuum to provide the title compound of Step I (26.1 g, 73.2 mmol, 73%). 1H NMR (400 MHz, DMSO-d6) δ 7.74 (s, 1H), 6.67 (s, 1H), 3.88 (s, 3H), 3.27 (d, J=12.3 Hz, 2H), 3.10-3.20 (m, 2H), 2.96 (s, 3H), 2.68 (t, J=11.3 Hz, 2H), 2.17 (s, 3H), 1.79 (d, J=11.2 Hz, 2H), 1.62-1.73 (m, 2H), 1.46-1.60 (m, J=10.7, 7.0, 3.5, 3.5 Hz, 1H), 1.31 (qd, J=11.9, 3.5 Hz, 2H).

1. additionvia addition funnel over the period of an hour
2. filtrationThe resultant precipitate was filtered
3. washwashed with EtOAc
4. customThe layers of the filtrate were separated
5. washthe aqueous layer was washed with EtOAc (3×)
6. dissolutionThe filtered solids were dissolved with DCM and H2O
7. customthe layers were separated
8. washThe organic layer was washed with DCM (2×)
9. dry with materialThe combined organic layer was dried (MgSO4)
10. filtrationfiltered
11. customThe resultant solid was triturated with diethyl ether
12. filtrationfiltered
13. customdried under vacuum