1-Hydroxybenzotriazole → 6-((S)-2-methyl-pyrrolidine-1-carbonyl)-3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazine-8-carboxylic acid ethyl ester

Participants

Reaction Conditions

Reaction Steps

To a solution of 3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazine-6,8-dicarboxylic acid 8-ethyl ester (Comp. No. 5a) (6.09 g, 25.5 mmol) in dimethylformamide (60 ml) was added 1-hydroxybenzotriazole (3.785 g, 0.028 mol) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (5.37 g, 28 mmol). The mixture was stirred for 1 h at 50° C., then (S)-2-methylpyrrolidine (2.385 g, 28 mmol) was added and the mixture was stirred at 25° C. overnight. Solvents were evaporated, the residue was dissolved in dichloromethane and washed against saturated aqueous sodium hydrogencarbonate to give 7.8 g (100%) of 6-((S)-2-methyl-pyrrolidine-1-carbonyl)-3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazine-8-carboxylic acid ethyl ester. LC/MS (method 2): Rt=1.06 min; m/z=307.19 (M+H+).

Provenance & Evidence