Methane → Perindopril

Participants

Reaction Steps

To a solution of N-[2-(ethoxycarbonyl)butyl]-N-ethoxycarbonylalanine (10.1 g, 35 mmol) in dichloromethane (35 mL) thionyl chloride (4.2 mL, 6.9 g, 58 mmol) was added in drops at 0-5° C. It was stirred at ambient temperature for 2-3 h. The solvent was evaporated to give a reddish oil. The residue was dissolved in THF (37.5 mL) and it was added to a suspension of perhydroindole-2-carboxylic acid (4.7 g, 28 mmol) in THF (37.5 mL). The suspension was refluxed with stirring for 4-4.5 h until a brownish solution was formed. After evaporation of the solvent the residue was dissolved in ethyl acetate (120 mL), t-butylamine (2.8 mL, 1.95 g, 27 mmol) in ethyl acetate (60 mL) was added slowly to the stirred solution resulting in separation of a crystalline mass. The mixture was heated until a solution was formed, then treated with charcoal. The crystalline product obtained after cooling was filtered to give perindopril eburmine (6.8 g, 55%).

Provenance & Evidence