反应详情

Methanesulfonic acid 4-(4-benzyloxycarbonylamino-3-fluoro-phenyl)-cyclohex-3-enyl ester (200 mg, 0.47 mmol, 1 equiv.) was dissolved in 5 mL of anhydrous acetonitrile. This solution was transferred into a flask containing (S)-2-methyl-pyrrolidine (159 mg, 1.88 mmol, 4 equiv.) and K2CO3 (285 mg, 2.07 mmol, 4.4 equiv.). The suspension was de-aerated by vacuum/nitrogen exchange 3 times, and then, heated on an oil bath set at 80° C. externally with stirring under nitrogen for 16 h. TLC (5% MeOH in DCM for SM) showed the reaction is complete. Acetonitrile was removed in vacuo. The residue was taken in water (5 mL) and DCM (10 mL). The two layers were separated and the aqueous layer was extracted with DCM (2×10 mL). The combined extracts were washed with NaHCO3 aq. (5 mL), brine (5 mL) and dried (K2CO3). The solution was filtered. The filtrate was concentrated in vacuo to obtain a crude product. The crude product was purified on a silica gel column, eluted with DCM, followed by 5% MeOH in DCM and 5% of 7N NH3-MeOH in DCM. The combined fractions containing the product were concentrated to yield the title compound.

1. customThis solution was transferred into a flask
2. temperatureheated on an oil bath
3. customset at 80° C.
4. customAcetonitrile was removed in vacuo
5. customThe two layers were separated
6. extractionthe aqueous layer was extracted with DCM (2×10 mL)
7. washThe combined extracts were washed with NaHCO3 aq. (5 mL), brine (5 mL)
8. dry with materialdried (K2CO3)
9. filtrationThe solution was filtered
10. concentrationThe filtrate was concentrated in vacuo
11. customto obtain a crude product
12. customThe crude product was purified on a silica gel column
13. washeluted with DCM
14. additionThe combined fractions containing the product
15. concentrationwere concentrated