反应详情

To a reaction mixture comprising 3.6 g. of 4,9-dihydro-4-hexanoyl-9-methyl-10H-thieno[3,4-b][1,5]benzodiazepin-10-one in 100 ml. of tetrahydrofuran is added, over a 15 minute period, with stirring, in an ice bath, under nitrogen, 90 ml. of 1M-borane. The reaction mixture is then refluxed with stirring for 19 hours. The mixture is cooled in an ice bath and 30 ml. of 6N hydrochloric acid is added dropwise with stirring. The tetrahydrofuran is removed by distillation and 23 g. of sodium hydroxide pellets are carefully added in the cold with stirring. A 15 ml. portion of water is added and the mixture is extracted with three 150 ml. portions of benzene. The benzene extracts are combined, washed with water, dried over sodium sulfate, filtered and concentrated to an oil. This crude product is dissolved in 10 ml. of 20% methylene chloride in hexane and chromatographed on an alumina column, eluting with the same solvent system. The first 150 ml. of eluent is discarded, then 100 ml. fractions are collected. Fractions 1-5 are combined and concentrated to an oil. The oil is extracted with ether repeatedly. The ether extracts are combined, washed with water, dried over sodium sulfate, filtered and concentrated to a residue. The residue is dissolved in 10 ml. of ether and shaken with 25 ml. of 1N sodium hydroxide. The ether is washed with water, dried over sodium sulfate, filtered and concentrated to residue. This residue is dissolved in 25 ml. of methylene chloride and purified by chromatography on a magnesol column, eluting with methylene chloride. The eluant is concentrated giving the desired product as a dark amber oil.

1. temperatureThe reaction mixture is then refluxed
2. stirringwith stirring for 19 hours
3. temperatureThe mixture is cooled in an ice bath
4. stirringwith stirring
5. customThe tetrahydrofuran is removed by distillation and 23 g
6. additionof sodium hydroxide pellets are carefully added in the cold
7. stirringwith stirring
8. additionportion of water is added
9. extractionthe mixture is extracted with three 150 ml
10. washwashed with water
11. dry with materialdried over sodium sulfate
12. filtrationfiltered
13. concentrationconcentrated to an oil
14. dissolutionThis crude product is dissolved in 10 ml
15. customof 20% methylene chloride in hexane and chromatographed on an alumina column
16. washeluting with the same solvent system
17. customfractions are collected
18. concentrationconcentrated to an oil
19. extractionThe oil is extracted with ether repeatedly
20. washwashed with water
21. dry with materialdried over sodium sulfate
22. filtrationfiltered
23. concentrationconcentrated to a residue
24. dissolutionThe residue is dissolved in 10 ml
25. stirringof ether and shaken with 25 ml
26. washThe ether is washed with water
27. dry with materialdried over sodium sulfate
28. filtrationfiltered
29. concentrationconcentrated to residue
30. dissolutionThis residue is dissolved in 25 ml
31. customof methylene chloride and purified by chromatography on a magnesol column
32. washeluting with methylene chloride
33. concentrationThe eluant is concentrated