Реакция #83024

Уравнение реакции

5-hydroxy-7-chloro-1-[2-methoxy-4-(2methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzoazepine

dimethylaminopyridine

dimethylaminopyridine hydrochloride

acetic acid

N-tert-butoxy-carbonyl-L-methionine

dicyclohexylcarbodi-imide

→

5-(N-tert-butoxycarbonyl-L-methionyloxy)-7-chloro-1-[2-methoxy-4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzo-azepine

Растворители

chloroform

methanol

Условия реакции

Обработка

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

Методика

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.

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