Hydrochloric Acid → HCID 178491558, compound

Participants

Reaction Steps

To a suspension of the hydrazide compound in 5 ml of N,N-dimethylformamide were added successively 0.90 ml of a dry 5.1N-hydrogen chloride in N,N-dimethylformamide solution and 0.23 ml of isoamyl nitrite at -20° C. with stirring. After disappearance of hydrazide compound, the reaction mixture was cooled to -30° C., and then the reaction mixture was neutralized by adding 0.67 ml of triethylamine to prepare a solution of N-(4-methoxybenzyloxycarbonyl)-L-histidine azide. The cold azide solution was added dropwise to a solution of 350 mg of isopropyl (2RS,3S)-3-amino-2-hydroxy-5-methylhexanoate hydrochloride and 0.46 ml of triethylamine in 8 ml of dry N,N-dimethylformamide under ice-cooling, and the mixture was stirred for 16 hours. The reaction mixture was concentrated under reduced pressure, and to the residue was added a 5% aqueous sodium bicarbonate solution. The mixture was extracted with ethyl acetate, and the ethyl acetate layer was washed with a saturated sodium chloride aqueous solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified with silica gel flash column chromatography (eluent: chloroform/methanol=20:1 by volume) to obtain 325 mg of isopropyl (2RS,3S)-3-[N-(4-methoxybenzyloxycarbonyl)-L-histidyl]amino-2-hydroxy-5-methylhexanoate as a white powder. To a solution of 320 mg of the isopropyl ester compound in 46 ml of isopropyl alcohol were added 300 mg of p-toluenesulfonic acid (anhydride) and 48 mg of a 10% palladium charcoal. The mixture was hydrogenated under a hydrogen atmosphere at room temperature. After filtration of the reaction mixture, the filtrate was concentrated under reduced pressure to obtain 513 mg of isopropyl (2RS,3S)-3-(L-histidyl)amino-2-hydroxy-5-methylhexanoate.2p-toluene sulfonic acid salt as a white powder.

Provenance & Evidence