反应详情

To a solution of 1-(4-methylsulfanylbenzylamino)butan-2-ol (8.5 g) and 2-benzoyl-4-bromobenzoic acid (14.7 g) and 1-hydroxy-1H-benzotriazole (7.4 g) in DMF (100 ml) was added triethylamine (8.4 ml) and then WSC (11.5 g) was added at room temperature. The mixture was stirred at room temperature for 4 days. The solvent was evaporated under reduced pressure, and the residue was partitioned between dichloromethane and water, washed with 1N hydrochloric acid, aqueous sodium hydrogen carbonate and brine and dried by adding sodium sulfate. The solvent was evaporated under reduced pressure and the obtained residue was purified by silica gel column chromatography (n-hexane/ethyl acetate=4/1-+13/7). The resulting colorless amorphous form was dissolved in dimethyl sulfoxide (100 ml) and triethylamine (25.3 ml) was added. Under ice-cooling, pyridine sulfur trioxide complex (14.5 g) was added, and the mixture was stirred at room temperature for 8 hrs. Water (300 ml) was added, and the mixture was extracted with ethyl acetate and washed with 1N hydrochloric acid, aqueous sodium hydrogen carbonate and brine. Sodium sulfate was added to dry the mixture. The solvent was evaporated under reduced pressure and the obtained residue was purified by silica gel column chromatography (n-hexane/ethyl acetate=4/1→2/3). The obtained colorless amorphous form was dissolved in 0.1N potassium hydroxide-ethanol solution (75 ml) and heated under reflux for 12 hrs. 1N Hydrochloric acid (7.5 ml) was added and the mixture was stirred under ice-cooling for 1 hr. The crystals were collected by filtration and washed with 70% ethanol-water to give the title compound (6.58 g, 34%).

1. customThe solvent was evaporated under reduced pressure
2. customthe residue was partitioned between dichloromethane and water
3. washwashed with 1N hydrochloric acid, aqueous sodium hydrogen carbonate and brine
4. customdried
5. additionby adding sodium sulfate
6. customThe solvent was evaporated under reduced pressure
7. customthe obtained residue was purified by silica gel column chromatography (n-hexane/ethyl acetate=4/1-+13/7
8. dissolutionThe resulting colorless amorphous form was dissolved in dimethyl sulfoxide (100 ml)
9. additiontriethylamine (25.3 ml) was added
10. temperatureUnder ice-cooling
11. additionpyridine sulfur trioxide complex (14.5 g) was added
12. stirringthe mixture was stirred at room temperature for 8 hrs
13. additionWater (300 ml) was added
14. extractionthe mixture was extracted with ethyl acetate
15. washwashed with 1N hydrochloric acid, aqueous sodium hydrogen carbonate and brine
16. additionSodium sulfate was added
17. customto dry the mixture
18. customThe solvent was evaporated under reduced pressure
19. customthe obtained residue was purified by silica gel column chromatography (n-hexane/ethyl acetate=4/1→2/3)
20. dissolutionThe obtained colorless amorphous form was dissolved in 0.1N potassium hydroxide-ethanol solution (75 ml)
21. temperatureheated
22. temperatureunder reflux for 12 hrs
23. addition1N Hydrochloric acid (7.5 ml) was added
24. stirringthe mixture was stirred under ice-
25. temperaturecooling for 1 hr
26. filtrationThe crystals were collected by filtration
27. washwashed with 70% ethanol-water