Diisopropylethylamine → N-Carbobenzoxy-O-Benzyl-L-Aspartyl-L-Prolyl-L-Arginine

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Reaction Steps

Arginine hydrochloride (2.3 Kg) and 1-hydroxybenzotriazole hydrate (1.5 Kg) are dissolved in a mixture of distilled water (5-6 L) and dimethylformamide (10-12 L). The pH of the solution is adjusted to 7.0-7.5 by addition of diisopropylethylamine. N-carbobenzoxy-β-benzyl-L-aspartyl-L-proline p-nitrophenyl ester (5.8 Kg) is dissolved in dimethylformamide (5-10 L) and added, maintaining the pH of solution at 7.0-7.5 with diisopropylethylamine. The solution is stirred at 20°-30° C. until the pH remains constant. The solids are collected on a filter, rinsed with a mixture of dimethylformamide (20-25 L) and distilled water (20-25 L), followed by distilled water 20-30 L). The product is dissolved in acetic acid (12-15 L) and the solution is diluted with distilled water (50-60 L). The pH is adjusted to 4.0-4.5 by addition of dilute sodium hydroxide. The solids are collected on a filter and washed with distilled water followed by acetone and then dried below 60° C.

Provenance & Evidence