Methyl chloroformate → 1-benzyl 4-tert-butyl ((1S)-1-[(5-amino-1-methyl-1H-pyrazol-4-yl)carbamoyl]tetramethylene}biscarbamate

Participants

Reaction Steps

To a solution of (2S)-2-[(benzyloxycarbonyl)amino]-5-[(tert-butoxycarbonyl)amino]pentanoic acid (22.0 g) and triethylamine (6.7 g) in tetrahydrofuran (240 ml) was added methyl chloroformate (6.2 g) followed by stirring under ice-cooling for 30 minutes. To the reaction mixture was added a solution of 1-methyl-1H-pyrazole-4,5-diamine sulfate (12.6 g) and triethylamine (13.4 g) in water (50 ml) at the same temperature. The mixture was stirred at the room temperature for 1 hour. To the reaction mixture was added chloroform (240 ml), and the layers were separated. The organic layer was washed successively with 10% aqueous citric acid solution, brine and saturated aqueous sodium hydrogencarbonate solution. The organic layer was dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo to give a crude product of 1-benzyl 4-tert-butyl {(1S)-1-[(5-amino-1-methyl-1H-pyrazol-4-yl)carbamoyl]tetramethylene}biscarbamate as an oil. The crude product was used directly in the next step without further purification.

Provenance & Evidence