反应详情

Sodium hydride (5.8 g) was added to a solution of 1,1-dimethylethyl 1-piperidine-4-methanolcarboxylate (25 g) in THF (800 ml). The mixture was stirred and refluxed for 3 hours (H2 gas evolution), then cooled (solution I). 1,1′-Carbonylbis-1H-imidazole (19.5 g) was added to a suspension of 4-amino-5-chloro-2-methoxybenzoic acid (24 g) in ACN (800 ml), stirred at room temperature. This mixture was stirred for 2 hours at room temperature (solution II). At room temperature, solution (II) was poured out into solution (I) and the reaction mixture was stirred for 20 hours at room temperature. Water (±10 ml) was added. The organic solvent was evaporated. The residue was partitioned between DCM and H2O. The insoluble solid was filtered off. The organic layer was separated, dried, filtered and the solvent was evaporated. The residue was crystallized from ACN (0° C.). The precipitate was filtered off and dried, filtered and the solvent was evaporated. The residue was crystallized from ACN. The precipitate was filtered off and dried (vacuum; 50° C.), yielding 20 g (42%) 1,1-dimethylethyl 4-[[(4-amino-5-chloro-2-methoxy-benzoyl)oxy]methyl]-1-piperidine-carboxylate (intermediate 10).

1. temperaturerefluxed for 3 hours (H2 gas evolution)
2. stirringstirred at room temperature
3. stirringthe reaction mixture was stirred for 20 hours at room temperature
4. customThe organic solvent was evaporated
5. customThe residue was partitioned between DCM and H2O
6. filtrationThe insoluble solid was filtered off
7. customThe organic layer was separated
8. customdried
9. filtrationfiltered
10. customthe solvent was evaporated
11. customThe residue was crystallized from ACN (0° C.)
12. filtrationThe precipitate was filtered off
13. customdried
14. filtrationfiltered
15. customthe solvent was evaporated
16. customThe residue was crystallized from ACN
17. filtrationThe precipitate was filtered off
18. customdried (vacuum; 50° C.)