反应详情

An 11.8 g. portion of 4,9-dihydro-10H-thieno[3,4-b][1,5]benzodiazepin-10-one is combined with 2.8 g. of 50% sodium hydride in mineral oil and 175 ml. of dimethylformamide and stirred for 2 hours. A 15.7 g. (11 ml.) portion of n-hexyl iodide is added and the mixture is stirred overnight. The reaction mixture is poured into ice water and the brown oil is separated and dissolved in methylene chloride. The dimethylformamide-water mixture is extracted twice with methylene chloride. All methylene chloride portions are combined, washed with water, dried over sodium sulfate, filtered and concentrated to a dark brown oil. This oil is dissolved in 10 ml. of methylene chloride and chromatographed on an alumina column. The column is eluted with 500 ml. of hexane followed by 30% methylene chloride in hexane for fractions 5-13 and methylene chloride:hexane (50:50) for fractions 14-19. Fraction 6 is concentrated to a dark brown viscous oil (A). Fractions 7-19 are combined and concentrated to dryness (B). (A) and (B) both crystallize in hexane and are combined, filtered, washed with hexane and dried. The product is dissolved with warming in 50 ml. of benzene and filtered. To the filtrate is added 100 ml. of hexane and the mixture is cooled overnight. The solid is collected, washed with ether and dried, giving the desired product, mp. 100°-102° C.

1. customthe brown oil is separated
2. dissolutiondissolved in methylene chloride
3. extractionThe dimethylformamide-water mixture is extracted twice with methylene chloride
4. washwashed with water
5. dry with materialdried over sodium sulfate
6. filtrationfiltered
7. concentrationconcentrated to a dark brown oil
8. dissolutionThis oil is dissolved in 10 ml
9. customof methylene chloride and chromatographed on an alumina column
10. washThe column is eluted with 500 ml
11. concentrationFraction 6 is concentrated to a dark brown viscous oil (A)
12. concentrationconcentrated to dryness (B)
13. custom(A) and (B) both crystallize in hexane
14. filtrationfiltered
15. washwashed with hexane
16. customdried
17. dissolutionThe product is dissolved
18. temperaturewith warming in 50 ml
19. filtrationof benzene and filtered
20. additionTo the filtrate is added 100 ml
21. temperatureof hexane and the mixture is cooled overnight
22. customThe solid is collected
23. washwashed with ether
24. customdried