反应详情

In 15 ml of chloroform were dissolved 0.7 g of 5-hydroxy-7-chloro-1-[2-methoxy-4-(2methylbenzoylamino)-benzoyl]-2,3,4,5-tetrahydro-1H-benzoazepine, 0.83 g of dimethylaminopyridine and 0.72 g of dimethylaminopyridine hydrochloride. Thereto were added 0.56 g of N-tert-butoxy-carbonyl-L-methionine and 0.93 g of dicyclohexylcarbodi-imide. The mixture was stirred at room temperature for 3 hours. 3 ml of methanol and 0.7 ml of acetic acid were added, and the mixture was stirred at room temperature for 30 minutes. The resulting insolubles were removed by filtration. The filtrate was mixed with a 5% aqueous sodium hydrogensulfate solution, followed by extraction with dichloromethane. The dichloromethane layer was washed with a saturated aqueous sodium hydrogencarbonate solution and a saturated aqueous sodium chloride solution in this order and dried over magnesium sulfate. The resulting dichloromethane solution was concentrated for solvent removal. The residue was purified by silica gel column chromatography [elutant: dichloromethane/methanol=150/1] to obtain 1.27 g of 5-(N-tert-butoxycarbonyl-L-methionyloxy)-7-chloro-1-[2-methoxy-4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzo-azepine.

1. stirringthe mixture was stirred at room temperature for 30 minutes
2. customThe resulting insolubles were removed by filtration
3. additionThe filtrate was mixed with a 5% aqueous sodium hydrogensulfate solution
4. extractionfollowed by extraction with dichloromethane
5. washThe dichloromethane layer was washed with a saturated aqueous sodium hydrogencarbonate solution
6. dry with materiala saturated aqueous sodium chloride solution in this order and dried over magnesium sulfate
7. concentrationThe resulting dichloromethane solution was concentrated for solvent removal
8. customThe residue was purified by silica gel column chromatography [elutant: dichloromethane/methanol=150/1]