Trifluoroacetic acid → (2R,4S,5S)-5-Amino-6-[2,2-dimethyl-4-(5-fluoro-2-methylphenyl)-5-oxopiperazin-1-yl]-4-hydroxy-2-methylhexanoic acid cyclohexylamide hemifumarate

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Reaction Steps

0.78 ml of trifluoroacetic acid (10.1 mmol) was added to a solution of 195 mg of {(1S,2S,4R)-4-(cyclohexylcarbamoyl)-1-[2,2-dimethyl-4-(5-fluoro-2-methylphenyl)-5-oxopiperazin-1-ylmethyl]-2-hydroxypentyl}carbamic acid t-butyl ester obtained in Example (105a) (0.34 mmol) in methylene chloride (1.6 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=100/10/1). 17 mg of fumaric acid (0.14 mmol) was added to a solution of 136 mg of (2R,4S,5S)-5-amino-6-[2,2-dimethyl-4-(5-fluoro-2-methylphenyl)-5-oxopiperazin-1-yl]-4-hydroxy-2-methylhexanoic acid cyclohexylamide obtained above (0.28 mmol) in methanol (3 ml), and the mixture was stirred at room temperature for five minutes. The reaction mixture was concentrated under reduced pressure, and methylene chloride (0.5 ml) was added to the residue. Diisopropyl ether (5 ml) was further added and the solid was collected by filtration to obtain 137 mg of the title compound (yield: 84%).

Provenance & Evidence