反应详情

110 g (0.24 M) of (S)-benzyl-{1-[[2-(o-fluorobenzoyl)-4-nitrophenyl]carbamoyl]ethyl}carbamate are dissolved in 400 ml of 30-33% hydrogen bromide solution in glacial acetic acid. 30 ml of methylene chloride are added thereto, the mixture is stirred at room temperature for 45 minutes, concentrated, treated with water and extracted 2-3 times with ether. The aqueous solution is cooled in ice, neutralised with solid sodium bicarbonate, extracted with methylene chloride, dried over sodium sulphate, filtered and concentrated. The residue is treated with 50 ml of glacial acetic acid and 500 ml of toluene. The mixture is heated to reflux for 15 to 20 minutes and evaporated. The residual oil is dissolved in methylene chloride and the solution obtained is washed with saturated sodium bicarbonate solution, dried over sodium sulphate, filtered and concentrated. The residue is dissolved in 400 ml of benzene and seeded with rac-5-(o-fluorophenyl)-1,3-dihydro-3-methyl-7-nitro-2H-1,4-benzodiazepin-2-one. The mixture is left to stand at room temperature overnight, 2 g of racemate crystallising out. The mother liquor is concentrated and treated with ether. By crystallisation from ether there is obtained (S)-5-(o-fluorophenyl)-1,3-dihydro-3-methyl-7-nitro-2H-1,4-benzodiazepin-2-one which melts at 130°-134° C.; [α]25D =+377.2° (in methylene chloride; 1%).

1. concentrationconcentrated
2. additiontreated with water
3. extractionextracted 2-3 times with ether
4. temperatureThe aqueous solution is cooled in ice
5. extractionextracted with methylene chloride
6. dry with materialdried over sodium sulphate
7. filtrationfiltered
8. concentrationconcentrated
9. additionThe residue is treated with 50 ml of glacial acetic acid and 500 ml of toluene
10. temperatureThe mixture is heated
11. temperatureto reflux for 15 to 20 minutes
12. customevaporated
13. dissolutionThe residual oil is dissolved in methylene chloride
14. customthe solution obtained
15. washis washed with saturated sodium bicarbonate solution
16. dry with materialdried over sodium sulphate
17. filtrationfiltered
18. concentrationconcentrated
19. dissolutionThe residue is dissolved in 400 ml of benzene
20. waitThe mixture is left
21. waitto stand at room temperature overnight
22. custom2 g of racemate crystallising out
23. concentrationThe mother liquor is concentrated
24. additiontreated with ether
25. customBy crystallisation from ether