Trifluoroacetic acid → (2S,4S,5S)-5-Amino-6-[2,2-dimethyl-4-(5-fluoro-2-methylphenyl)-5-oxopiperazin-1-yl]-4-hydroxy-2-isopropylhexanoic acid (2,2-dimethylpropyl)amide hemifumarate

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Reaction Steps

0.69 ml of trifluoroacetic acid (8.96 mmol) was added to a solution of 177 mg of {(1S,2S,4S)-4-(2,2-dimethylpropylcarbamoyl)-1-[2,2-dimethyl-4-(5-fluoro-2-methylphenyl)-5-oxopiperazin-1-ylmethyl]-2-hydroxy-5-methylhexyl}carbamic acid t-butyl ester obtained in Example (70g) (0.30 mmol) in methylene chloride (1.4 ml) at room temperature, and the mixture was stirred at the same temperature for 30 minutes. The reaction mixture was concentrated under reduced pressure and diluted with a saturated sodium bicarbonate aqueous solution, 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=100/10/1). 14 mg of fumaric acid (0.12 mmol) was added to a solution of 122 mg of the resulting (2S,4S,5S)-5-amino-6-[2,2-dimethyl-4-(5-fluoro-2-methylphenyl)-5-oxopiperazin-1-yl]-4-hydroxy-2-isopropylhexanoic acid (2,2-dimethylpropyl)amide (0.25 mmol) in methanol (2 ml), and the mixture was stirred at room temperature for five minutes. The solvent was evaporated under reduced pressure to obtain 100 mg of the title compound (yield: 74%).

Provenance & Evidence