反应详情

2-(Morpholino)ethylamine (20 g) was heated at 175°-180° C. and 1-(4-chlorophenyl)cyclobutyl-2-methoxyethanone (20 g) prepared as described in Example 206 was added dropwise with stirring over 1 hour. The mixture was stirred at 180° C. for a further hour. A stream of nitrogen was passed through the reaction mixture to remove any water formed. The mixture was cooled and added dropwise to a suspension of sodium borohydride (10 g) in propan-2-ol (800 ml). The mixture was then heated under reflux for 3 hours. Propan-2-ol was evaporated and an ice/water mixture was added to the residue which was cooled and acidified with 5N hydrochloric acid. The acidified mixture was basified and extracted with ether. Hydrogen chloride gas was passed into the dried extract which was then evaporated to dryness. The residue was heated with propan-2-ol, filtered and the filtrate evaporated to dryness. The residue was partitioned between ether and 2N hydrochloric acid. The acid layer was washed with ether, basified and extracted with ether. Hydrogen chloride gas was passed into the ether extract which was then evaporated to dryness to give a residue which was recrystallised from propan-2-ol to give N-(2-morpholinoethyl)-1-[1-(4-chlorophenyl)cyclobutyl]-2-methoxyethylamine dihydrochloride (m.p. 234°-237° C.).

1. additionwas added dropwise
2. stirringThe mixture was stirred at 180° C. for a further hour
3. customto remove any water
4. customformed
5. temperatureThe mixture was cooled
6. temperatureThe mixture was then heated
7. temperatureunder reflux for 3 hours
8. customPropan-2-ol was evaporated
9. additionan ice/water mixture was added to the residue which
10. temperaturewas cooled
11. extractionextracted with ether
12. extractionextract which
13. customwas then evaporated to dryness
14. temperatureThe residue was heated with propan-2-ol
15. filtrationfiltered
16. customthe filtrate evaporated to dryness
17. customThe residue was partitioned between ether and 2N hydrochloric acid
18. washThe acid layer was washed with ether
19. extractionextracted with ether
20. extractionextract which
21. customwas then evaporated to dryness
22. customto give a residue which
23. customwas recrystallised from propan-2-ol