Dimethyl Sulfoxide → HCID 10862657, compound

Participants

Reaction Conditions

Reaction Steps

A 649 mg (1.8 mmol) portion of (3R)-1-benzyloxycarbonyl-3-(1-tert-butoxycarbonylaminomethylcyclopropyl)pyrrolidine was dissolved in 20 ml of methanol to which was subsequently added 200 mg of 5% (v/v) palladium-carbon to carry out 2 hours of hydrogenation under normal pressure with warming by an infrared lamp. After completion of the reaction, 5% (v/v) palladium-carbon was removed by filtration and methanol was evaporated. The resulting residue was dissolved in 20 ml of dimethyl sulfoxide to which were subsequently added 2 ml of triethylamine and 312 mg (1 mmol) of 5-amino-6,7-difluoro-[(1R,2S)-2-fluorocyclopropyl]-1,4-dihydro-8-methyl-4-oxoquinoline-3-carboxylic acid, followed by 18 hours of stirring at 150° C. After completion of the reaction, dimethyl sulfoxide was evaporated, and the resulting residue was mixed with 100 ml of chloroform and washed with 10% citric acid (100 ml×1) and saturated brine (100 ml×1) in that order. The organic layer was dried over anhydrous sodium sulfate, and the solvent was evaporated. A 10 ml portion of concentrated hydrochloric acid was added dropwise to the resulting residue under ice cooling, followed by 1 hour of stirring at room temperature. After completion of the reaction, the reaction solution was washed with dichloromethane (20 ml×1). The aqueous layer was adjusted to pH 12 with sodium hydroxide aqueous solution and then to pH 7.4 with hydrochloric acid, followed by extraction with chloroform (100 ml×4). The organic layers were combined and dried over anhydrous sodium sulfate, and then the solvent was evaporated. The resulting residue was subjected to a silica gel thin layer chromatography, and the silica gel collected after development by the lower layer of a mixture solvent system of chloroform:methanol:water=7:3:1 was extracted with the same solvent. Thereafter, the thus obtained crude product was recrystallized from chloroform-isopropyl ether to afford 101.5 mg (24%) of the title compound.

Provenance & Evidence