Trifluoroacetic acid → (S)-4-benzyloxycarbonylaminoacetyl-3-{3-(6-tert-butoxycarbonylaminohexanoylamino)propyl}-2-oxopiperazine-1-acetic acid

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Reaction Steps

In 3.0 cc of trifluoroacetic acid was dissolved (S)-4-benzyloxycarbonylaminoacetyl-3-(3-t-butoxycarbonylaminopropyl)-2-oxopiperazine-1-acetic acid t-butyl ester (0.6 g, 1.07 mmol) produced in Reference Example 2. The solution was stirred for 30 minutes at room temperature, which was concentrated under reduced pressure. In 2.1 cc of DMF were dissolved 6-t-butoxyaminocaproic acid (0.26 g, 1.12 mmol), 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride (0.22 g, 1.14 mmol) and 1-hydroxybenzotriazole (0.15 g, 1.12 mmol). The solution was stirred for one hour, to which was added 2.1 cc of a DMF solution of the concentrate obtained above and triethylamine (0.3 cc, 2.14 mmol). The mixture was stirred for 4 hours at room temperature. The reaction mixture was diluted with ethyl acetate, which was 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, which was purified by means of a silica gel column chromatography (ethyl acetate/methanol/acetic acid=20/10/0.6) to afford 0.42 g (y. 63.3%) of the titled compound as a colorless amorphous powdery product.

Provenance & Evidence