反应详情

A mixture of ethyl 4-[[[(7-chloro-2,3-dihydro-1,4-benzodioxin-5-yl)carbonyl]-amino]methyl]-3-methoxy-1-piperidinecarboxylate (0.051 mol) and potassium hydroxide (0.5 mol) in ethanol (200 ml) was stirred and refluxed for 30 hours and then cooled. The solvent was evaporated. The residue was dissolved in water and the solvent was evaporated again. The residue was partitioned between DCM and water. The organic layer was separated, dried, filtered, and the solvent was evaporated. The residue was purified by column chromatography over silica gel (eluent : CH2Cl2/(CH3OH/NH3)93/7). The pure fractions were collected and the solvent was evaporated, yielding 9 g of (cis)-7-chloro-2,3-dihydro-N-[(3-methoxy-4-piperidinyl)methyl]-1,4-benzodioxin-5-carboxamide (interm. 3-i). Part of interm. (3-i) was dissolved in 2-propanol and converted into the ethanedioic acid salt (1:1). The precipitate was filtered off and dried, yielding 1.2 g of (cis)-7-chloro-2,3-dihydro-N-[(3-methoxy4-piperidinyl)methyl]-1,4-benzodioxin-5-carboxamide ethanedioate (1:1) (interm. 3-j, mp. 208° C.).

1. temperaturerefluxed for 30 hours
2. temperaturecooled
3. customThe solvent was evaporated
4. dissolutionThe residue was dissolved in water
5. customthe solvent was evaporated again
6. customThe residue was partitioned between DCM and water
7. customThe organic layer was separated
8. customdried
9. filtrationfiltered
10. customthe solvent was evaporated
11. customThe residue was purified by column chromatography over silica gel (eluent : CH2Cl2/(CH3OH/NH3)93/7)
12. customThe pure fractions were collected
13. customthe solvent was evaporated