Hydrogenation

Abstract

A solution of benzyloxycarbonyl-l-prolyl-l-leucyl-glycinamide [3] (41.8 g, 100 mmol) in methanol [4] (250 ml) is prepared in a 500-ml round bottom flask [5] provided with a magnetic stirrer, a gas inlet-outlet tube [6] and surrounded by a large evaporating dish [7]. The air is displaced by a slow stream of nitrogen and a 10% palladium-on-charcoal catalyst [8] (4.2 g = 0.42 g metal) is added. Once again a slow stream of nitrogen is led through the flask, for a few minutes, then the introduction of a slow stream of hydrogen is started. The catalyst is kept in suspension by vigorous stirring. The gas which escapes through the outlet tube [9] is led, from time to time, through a half-saturated filtered solution of Ba(OH)₂ in water. When the evolution of CO₂ ceases the reaction mixture is warmed by a water bath of about 50 °C until no more CO₂ can be detected [10] in the escaping gas. The reaction mixture is cooled to room temperature and the introduction of hydrogen is terminated. The remaining gas is displaced by nitrogen and the catalyst is removed by filtration [11], preferably under a blanket of nitrogen. The catalyst is washed with methanol (50 ml) and stored under water until it is discarded or regenerated. The filtrate is evaporated in vacuo [12] or under a stream of air in a well ventilated hood. The residue is dried in air and finally in a desiccator over P₂O₅ in vacuo. The tripeptide amide (hemihydrate) weighs 28.8 g (98%) and melts at 125–126 °C [13].