Hydrochloric Acid → (R,S)-[4-[2-(4-Fluorobenzoylamino)-4-oxo-4-(4-pyridin-4-ylpiperazin-1-yl)butyryl]-3-methoxycarbonylmethyl-2-oxopiperazin-1-yl]acetic Acid

Participants

Reaction Steps

To a mixture of (R,S)-[4-[2-amino-4-oxo-4-[4-(pyridin-4-yl)piperazin-1-yl]butyryl]-3-methoxy-carbonylmethyl-2-oxopiperazin-1-yl]acetic acid trifluoroacetic acid salt (0.25 g) produced in Working Example 21, an aqueous solution of sodium hydrogen carbonate (0.15 g), water (2.5 ml) and 1,4-dioxane (2.5 ml) was added 4-fluorobenzoyl chloride (0.051 ml) and the solution was stirred for 1 hour at room temperature. The pH of the reaction solution was adjusted to 3 with 1N hydrochloric acid and the solution was concentrated under reduced pressure. The concentrate was purified by means of CHP-20 column chromatography (eluent:H2O→15% acetonitrile aqueous solution→20% acetonitrile aqueous solution→25% acetonitrile aqueous solution→30% acetonitrile aqueous solution). The objected fraction was concentrated and subjected to lyophilization to give the titled compound (0.10 g) as a white amorphous powdery product.

Provenance & Evidence