反应详情

A brown solution of Intermediate 24b (855 mg, 4.98 mmol) and 4-hydroxypiperidine (2.02 g, 19.9 mmol) in DMA (15 mL) was irradiated to 175° C. in the microwave for 3 h. The cooled solution was concentrated in vacuo, then the residue diluted with water (20 mL) and brine (20 mL). The mixture was washed with diethyl ether (2×50 mL), then extracted with EtOAc (2×50 mL). The combined EtOAc layers were washed with brine (50 mL), dried (Na2SO4), filtered and concentrated in vacuo to leave a yellow oil. The aqueous was further extracted with DCM (3×50 mL). The combined DCM layers were passed through a hydrophobic frit and concentrated in vacuo to leave a brown oil. The two oils were combined. FCC, using 4-5% [2M NH3 in MeOH] in DCM, gave the title compound as a yellow crystalline solid (514 mg, 44%). LCMS (Method 3): Rt 1.96 min, m/z 237 [MH+].

1. concentrationThe cooled solution was concentrated in vacuo
2. additionthe residue diluted with water (20 mL) and brine (20 mL)
3. washThe mixture was washed with diethyl ether (2×50 mL)
4. extractionextracted with EtOAc (2×50 mL)
5. washThe combined EtOAc layers were washed with brine (50 mL)
6. dry with materialdried (Na2SO4)
7. filtrationfiltered
8. concentrationconcentrated in vacuo
9. customto leave a yellow oil
10. extractionThe aqueous was further extracted with DCM (3×50 mL)
11. concentrationconcentrated in vacuo
12. customto leave a brown oil