Ethylene Glycol → HCID 19823733, compound

A mixture of 2-{4-[1-(4-chlorophenyl)cyclobutyl]-4-dimethylaminobutoxy}-N,N-3-oxapentamethyleneacetamide (4.9 g prepared as described in Example 214), ethylene glycol (30 ml) and 18N aqueous sodium hydroxide solution (10 ml) was heated under reflux for 21/2 hours and then cooled. Water (30 ml) was added and the aqueous mixture washed with ether. The ether extracts were washed with 5N aqueous sodium hydroxide solution and the alkaline washings combined with the aqueous reaction mixture and the resulting mixture neutralised by addition of concentrated hydrochloric acid. The neutralised mixture was evaporated and the residue dried by azeotropic distillation with methanol and then propan-2-ol. The residue was mixed with propan-2-ol and the mixture filtered. The filtrate was evaporated and the residue was heated at 63°/0.7 mm to remove excess ethyleneglycol and then dissolved in ethanol (50 ml). Thionyl chloride (3.5 ml) was added dropwise with stirring and the mixture allowed to stand for 16 hours under anhydrous conditions. The reaction mixture was then poured into a mixture of ice and excess aqueous sodium bicarbonate solution. The mixture was extracted with ether and the extracts were dried and evaporated to give an oil which was mixed with ether. The mixture was filtered and a solution of maleic acid in ether was added to the filtrate to produce a gum. The supernatent was decanted and the residual gum washed with ether, which was decanted, several times and then basified with sodium bicarbonate. The product was extracted with ether and the extracts were dried and evaporated to give ethyl 2-{4-[1-(4-chlorophenyl)-cyclobutyl]-4-dimethylaminobutoxy}acetate. A sample of this material (2.8 g) was dissolved in methanol (300 ml). Ammonia gas was bubbled into the solution which was cooled in ice, saturated with ammonia gas and then evaporated and heated at 90°/20 mm to leave 2-{4-[1-(4-chlorophenyl)cyclobutyl]-4-dimethylaminobutoxy}acetamide a residual oil the boiling point of which was not determined.

1. temperaturewas heated
2. temperatureunder reflux for 21/2 hours
3. temperaturecooled
4. washthe aqueous mixture washed with ether
5. washThe ether extracts were washed with 5N aqueous sodium hydroxide solution
6. additionthe resulting mixture neutralised by addition of concentrated hydrochloric acid
7. customThe neutralised mixture was evaporated
8. dry with materialthe residue dried by azeotropic distillation with methanol
9. additionThe residue was mixed with propan-2-ol
10. filtrationthe mixture filtered
11. customThe filtrate was evaporated
12. temperaturethe residue was heated at 63°/0.7 mm
13. customto remove excess ethyleneglycol
14. dissolutiondissolved in ethanol (50 ml)
15. additionThionyl chloride (3.5 ml) was added dropwise
16. additionThe reaction mixture was then poured into a mixture of ice and excess aqueous sodium bicarbonate solution
17. extractionThe mixture was extracted with ether
18. customthe extracts were dried
19. customevaporated
20. customto give an oil which
21. filtrationThe mixture was filtered
22. additiona solution of maleic acid in ether was added to the filtrate
23. customto produce a gum
24. customThe supernatent was decanted
25. washthe residual gum washed with ether, which
26. customwas decanted
27. extractionThe product was extracted with ether
28. customthe extracts were dried
29. customevaporated

ORD record

ord-2f60df99bf8245bcb0049b52108dbfd0

Source dataset

uspto-grants-1991_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05047432