Oxalic Acid → (s)-3-(3-t-Butoxycarbonylaminopropyl)-2-oxopiperazine-1-acetic acid t-butyl ester oxalate

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Reaction Steps

In 54.6 cc of acetone were dissolved (2,2-dimethoxyethyl)aminoacetic acid t-butyl ester (6.0 g, 27.7 mmol) and N--Z--Orn(Boc)--OH (10.0 g, 27.7 mmol). To the solution was added, at 15° C. under stirring, 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride (5.6 g, 29.2 mmol). The mixture was stirred for one hour at room temperature, and concentrated under reduced pressure. The concentrate was dissolved in ethyl acetate, and washed with a 5% aqueous solution of potassium hydrogensulfate and a saturated aqueous solution of sodium hydrogencarbonate. The organic layer was concentrated under reduced pressure to give a pale yellow oily substance. This oily substance and p-toluenesulfonic acid 1.0 hydrate (1.04 g, 5.46 mmol) were dissolved in 137 cc of toluene, and the solution was stirred for two hours at 70° C. The reaction mixture was poured into a saturated aqueous solution of sodium hydrogencarbonate. The mixture was subjected to extraction with ethyl acetate. The organic layer was concentrated under reduced pressure, and purified by means of a silica gel column chromatography (hexane/ethyl acetate=3/2) to give 8.3 g of a pale yellow oily substance. This oily substance (8.3 g, 16.5 mmol) was dissolved in 166 cc of ethyl acetate, to which was added 1.7 g of 10% Pd-C, and then the mixture was stirred for two hours under hydrogen atmosphere. The catalyst was filtered off, and the filtrate was dissolved in 16.6 cc of methanol. To the solution was added oxalic acid 2.0 hydrate (2.1 g, 16.5 mmol), and the mixture was concentrated under reduced pressure. Resulting crystalline product was washed with ethyl acetate to afford 5.1 g (66.8%) of the titled compound as white crystals.

Provenance & Evidence