Trifluoroacetic acid → (2R,4S,5S)-5-Amino-6-[2,2-dimethyl-4-(2-methylphenyl)-5-oxopiperazin-1-yl]-2-ethyl-4-hydroxyhexanoic acid (2,2-dimethylpropyl)amide hemifumarate

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Reaction Steps

0.43 ml of trifluoroacetic acid (5.6 mmol) was added to a solution of 105 mg of {(1S,2S,4R)-4-(2,2-dimethylpropylcarbamoyl)-1-[2,2-dimethyl-4-(2-methylphenyl)-5-oxopiperazin-1-ylmethyl]-2-hydroxyhexyl}carbamic acid t-butyl ester obtained in Example (110c) (0.19 mmol) in methylene chloride (1.0 ml) at room temperature, and the mixture was stirred at the same temperature for 30 minutes. After concentration under reduced pressure, a saturated sodium bicarbonate aqueous solution was added to the reaction mixture, followed by extraction with methylene chloride. Then, the organic layer was dried over anhydrous magnesium sulfate. After filtration, the solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (elution solvent:methylene chloride/methanol/triethylamine=9/1/0-90/10/1). 9.7 mg of fumaric acid (0.08 mmol) was added to a solution of 77 mg of (2R,4S,5S)-5-amino-6-[4-(2-chlorophenyl)-2,2-dimethyl-5-oxopiperazin-1-yl]-4-hydroxy-2-methylhexanoic acid (2,2-dimethylpropyl)amide obtained above (0.17 mmol) in methanol (2 ml), and the mixture was stirred at room temperature for five minutes. The reaction mixture was concentrated under reduced pressure, and n-hexane (1 ml) was added to the residue. The solid was collected by filtration to obtain 69 mg of the title compound (yield: 71%).

Provenance & Evidence