反应详情

温度

200 °C

A finely divided mixture of 4-hydroxy-3-methoxyphenethylamine (9.9 g) and 1-phenylcyclopentane carboxylic acid (11.9 g) was heated at 200° C. under nitrogen for two hours. The melt was cooled slightly and added to a 1:1 mixture of glacial acetic acid and water. A solid crystallised which was removed by filtration and washed with acetic acid. The filtrate was basified with excess sodium carbonate and extracted with ether. The extract was washed with 4N hydrochloric acid. The ether extract yielded a residue which was heated under reflux in a nitrogen atmosphere with acetonitrile (156 ml) and phosphorus oxychloride (18.7 ml) for one hour. The solvent was removed and water was added to the residue. The mixture was warmed and ethanol was added. The resulting solution was heated at 90°-95° C. for one hour and cooled. Ethanol was added to dissolve any solid and the solution basified with aqueous ammonia solution. Sodium borohydride (2.5 g in total) was added portionwise and the solvents removed by evaporation. The residue was partitioned between water and ethyl acetate to give a solid which was collected by filtration, washed with water and dried in air. The solid was dissolved in a mixture of 37-40% aqueous formaldehyde solution (27 ml) and formic acid (15 ml) and the solution warmed to 60° C. for two hours. Ice was added and the mixture basified with aqueous ammonia solution. The resulting mixture was extracted with ether. The extract was dried and the solvent removed to give a residue which was dissolved in ether. The extract was filtered, dried and ethereal oxalic acid was added. A solid was deposited. The ether was removed by decantation and ethyl acetate was added and the mixture heated at reflux. The solid product was triturated under the ethyl acetate, collected by filtration washed with ethyl acetate and dried in air to give 7-hydroxy-6-methoxy-2-methyl-1-(1-phenylcyclopentyl-1,2,3,4-tetrahydroisoquinoline oxalate, m.p. 172° C. (dec).

1. temperatureThe melt was cooled slightly
2. customA solid crystallised which
3. customwas removed by filtration
4. washwashed with acetic acid
5. extractionextracted with ether
6. washThe extract was washed with 4N hydrochloric acid
7. extractionThe ether extract
8. customyielded a residue which
9. temperaturewas heated
10. customThe solvent was removed
11. additionwater was added to the residue
12. temperatureThe mixture was warmed
13. additionethanol was added
14. temperatureThe resulting solution was heated at 90°-95° C. for one hour
15. temperaturecooled
16. additionEthanol was added
17. dissolutionto dissolve any solid
18. additionSodium borohydride (2.5 g in total) was added portionwise
19. customthe solvents removed by evaporation
20. customThe residue was partitioned between water and ethyl acetate
21. customto give a solid which
22. filtrationwas collected by filtration
23. washwashed with water
24. customdried in air
25. dissolutionThe solid was dissolved in a mixture of 37-40% aqueous formaldehyde solution (27 ml) and formic acid (15 ml)
26. temperaturethe solution warmed to 60° C. for two hours
27. additionIce was added
28. extractionThe resulting mixture was extracted with ether
29. customThe extract was dried
30. customthe solvent removed
31. customto give a residue which
32. filtrationThe extract was filtered
33. customdried
34. additionethereal oxalic acid was added
35. customThe ether was removed by decantation and ethyl acetate
36. additionwas added
37. temperaturethe mixture heated
38. temperatureat reflux
39. customThe solid product was triturated under the ethyl acetate
40. filtrationcollected by filtration
41. washwashed with ethyl acetate
42. customdried in air