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

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Reaction Steps

(S)-4-benzyloxycarbonylaminoacetyl-3-(3-tert-butoxycarbonylaminopropyl)-2-oxopiperazine-1-acetic acid tert-butyl ester as obtained in Reference Example 2 (0.6 g, 1.07 mmol) was dissolved in 3.0 ml of trifluoroacetic acid, followed by stirring at room temperature for 30 minutes, after which the reaction mixture was concentrated under reduced pressure. Separately, 6-tert-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) were dissolved in 2.1 ml of DMF, followed by stirring for 1 hour. To this solution, of the above residue and 2.1 ml of a DMF solution comprising triethylamine (0.3 ml, 2.14 mmol) was added, followed by stirring at room temperature for 4 hours. The reaction mixture was diluted with ethyl acetate and washed with 5% aqueous potassium hydrogen sulfate and saturated aqueous sodium bicarbonate. The organic layer was concentrated under reduced pressure; the residue was purified by silica gel column chromatography (ethyl acetate/methanol/acetic acid=20/10/0.6) to yield 0.42 g (63.3%) of the title compound as a colorless amorphous powder.

Provenance & Evidence