Reacción #83024

Ecuación de reacción

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

Disolventes

chloroform

methanol

Condiciones de reacción

Tratamiento posterior

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

Procedimiento

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.

Fuente