反应详情

Reaction was carried out under a nitrogen atmosphere. Lithium hydride (95%) (0.036 mol) was suspended in THF (30 ml). A solution of 2-hydroxy-2-methyl-propanenitrile (0.036 mol) in TEF (10 ml) was added dropwise (evolution of hydrogen gas). The mixture was stirred for 90 minutes at room temperature. A solution of 7-oxa-3-azabicyclo[4.1.0]heptane-3-carboxylic acid, ethyl ester (0.03 mol) in THF (15 ml) for 90 minutes. The reaction mixture was cooled to 15 ° C. Diethyl sulfate (0.039 mol) was added (exothermic temperature rise to 25 ° C.). The reaction mixture was stirred for one hour at room temperature, then stirred and refluxed for 6 hours, cooled and a drop of water was added. The solvent was evaporated. The residue was partitioned between water and DCM. The organic layer was separated, dried, filtered and the solvent was evaporated. The residue was purified by column chromatography over silica gel (eluent: CH2C]2/CH3OH from 100/0 to 99/1). The pure fractions were collected and the solvent was evaporated, yielding 4.3 g of ethyl (trans)-4-cyano-3-ethoxy-1-piperidine-carboxylate (intermediate 13).

1. customReaction
2. temperatureThe reaction mixture was cooled to 15 ° C
3. stirringThe reaction mixture was stirred for one hour at room temperature
4. stirringstirred
5. temperaturerefluxed for 6 hours
6. temperaturecooled
7. customThe solvent was evaporated
8. customThe residue was partitioned between water and DCM
9. customThe organic layer was separated
10. customdried
11. filtrationfiltered
12. customthe solvent was evaporated
13. customThe residue was purified by column chromatography over silica gel (eluent: CH2C]2/CH3OH from 100/0 to 99/1)
14. customThe pure fractions were collected
15. customthe solvent was evaporated