反应详情

A mixture of the product of Example 208 in the form of its free base (2.0 g), 98% formic acid (8 ml) and 37-40% aqueous formaldehyde solution (25 ml) was stirred at room temperature for 2 hours. The mixture was then heated at 95°-100° C. for 18 hours, cooled, basified and extracted with ether. The extract was washed with water and dried. Dry hydrogen chloride gas was passed into the ethereal solution. Evaporation of the solvent gave a residue which was heated with ethyl acetate (20 ml) to give a white solid which was partitioned between ether and water. The aqueous phase was basified and then extracted with ether. The extract was dried and evaporated to give a residue which was distilled using a Buchi Kugelrohr apparatus (200° C./0.5 mm) to give N-methyl-N-(2-morpholinoethyl)-1-[1-(4-chlorophenyl)cyclobutyl]-2-methoxyethylamine.

1. temperatureThe mixture was then heated at 95°-100° C. for 18 hours
2. temperaturecooled
3. extractionextracted with ether
4. washThe extract was washed with water
5. customdried
6. customEvaporation of the solvent
7. customgave a residue which
8. customto give a white solid which
9. customwas partitioned between ether and water
10. extractionextracted with ether
11. customThe extract was dried
12. customevaporated
13. customto give a residue which
14. distillationwas distilled
15. customa Buchi Kugelrohr apparatus (200° C./0.5 mm)