反应详情

The compound prepared in the above (2) (5 g) and ethyl 3-aminobenzoate (4.3 g) are suspended in dichloromethane (25 ml), and thereto is added EDC.HCl (4.9 g). The mixture is stirred at room temperature for one hour. The reaction mixture is diluted with dichloromethane and washed with 10% hydrochloric acid, diluted aqueous sodium hydrogen carbonate solution and saturated aqueous sodium chloride solution in this order, dried over anhydrous sodium sulfate, and dichloromethane is distilled off under reduced pressure. The residue is dissolved in dichloromethane (25 ml) and thereto is added triethylamine (3.5 g) and further added dropwise methanesulfonyl chloride (3.9 g) with stirring under ice cooling, and the mixture is stirred at room temperature for one hour. The reaction mixture is diluted with dichloromethane and washed with 10% hydrochloric acid, diluted aqueous sodium hydrogen carbonate solution and saturated aqueous sodium chloride solution in this order, dried over anhydrous sodium sulfate, and dichloromethane is distilled off under reduced pressure. The residue is dissolved in ethanol (100 ml) and thereto is added potassium thioacetate (3.2 g), and the mixture is refluxed for 48 hours. Ethanol is distilled off under reduced pressure, and the residue is extracted with ethyl acetate. The extract is washed with 10% hydrochloric acid, diluted aqueous sodium hydrogen carbonate solution and saturated aqueous sodium chloride solution in this order, and ethyl acetate is distilled off under reduced pressure. The residue is dissolved in acetonitrile and purified by a medium pressure column chromatography with CHP-20P (eluant, water-acetonitrile). The fractions containing the desired compound are collected and concentrated into dryness under reduced pressure to give ethyl 3-[(3-acetylthio-2-benzylbutanoyl)amino]benzoate (1.4 g). IR (film; cm -1): 1720, 1690, 1660

1. washwashed with 10% hydrochloric acid, diluted aqueous sodium hydrogen carbonate solution and saturated aqueous sodium chloride solution in this order
2. dry with materialdried over anhydrous sodium sulfate, and dichloromethane
3. distillationis distilled off under reduced pressure
4. dissolutionThe residue is dissolved in dichloromethane (25 ml)
5. additionis added triethylamine (3.5 g)
6. additionfurther added dropwise methanesulfonyl chloride (3.9 g)
7. stirringwith stirring under ice cooling
8. stirringthe mixture is stirred at room temperature for one hour
9. additionThe reaction mixture is diluted with dichloromethane
10. washwashed with 10% hydrochloric acid, diluted aqueous sodium hydrogen carbonate solution and saturated aqueous sodium chloride solution in this order
11. dry with materialdried over anhydrous sodium sulfate, and dichloromethane
12. distillationis distilled off under reduced pressure
13. dissolutionThe residue is dissolved in ethanol (100 ml)
14. additionis added potassium thioacetate (3.2 g)
15. temperaturethe mixture is refluxed for 48 hours
16. distillationEthanol is distilled off under reduced pressure
17. extractionthe residue is extracted with ethyl acetate
18. washThe extract is washed with 10% hydrochloric acid, diluted aqueous sodium hydrogen carbonate solution and saturated aqueous sodium chloride solution in this order, and ethyl acetate
19. distillationis distilled off under reduced pressure
20. dissolutionThe residue is dissolved in acetonitrile
21. custompurified by a medium pressure column chromatography with CHP-20P (eluant, water-acetonitrile)
22. additionThe fractions containing the desired compound
23. customare collected
24. concentrationconcentrated into dryness under reduced pressure