Diisopropylethylamine → methyl 4-[(3-(pyridin-3-yl)pyrrolidin-1-yl)carbonyl]-3,4-dihydro-2H-1,4-benzoxazine-6-carboxylate

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Reaction Steps

1.8 g of methyl 3,4-dihydro-2H-1,4-benzoxazine-6-carboxylate, 93.2 ml of dichloromethane and 4.62 ml of diisopropylethylamine are placed in a 250 ml round-bottomed flask under a nitrogen atmosphere. 1.38 g of triphosgene are added at 0° C. and then the reaction mixture is left stirring at ambient temperature for three hours. 1.62 ml of diisopropylethylamine and 1.45 g of 3-(pyrrolidin-3-yl)pyridine are subsequently added and the reaction mixture is stirred for eighteen hours. A saturated aqueous sodium hydrogencarbonate solution and dichloromethane are added. The aqueous phase is extracted three times with dichloromethane. The organic phases are combined, washed with water and with a saturated aqueous sodium chloride solution and dried over sodium sulfate and then the solvent is evaporated under reduced pressure. The residue is chroratographed on silica gel with a dichloromethane/methanol 95/5 mixture. 2.39 g of methyl 4-[(3-(pyridin-3-yl)pyrrolidin-1-yl)carbonyl]-3,4-dihydro-2H-1,4-benzoxazine-6-carboxylate are obtained.

Provenance & Evidence