Dimethyl Sulfoxide → 218281-25-5

Participants

Reaction Steps

To a dimethyl sulfoxide (2 ml) solution of 1-cyclopropyl-6,7-difluoro-1,4-dihydro-8-methoxy-4-oxoquinoline-3carboxylic acid EF2 complex (345 mg, 1.00 mmol) were added 3-(S)-tert-butoxycarbonylamino-4-(S)-fluoromethylpyrrolidine (327 mg, 1.00 mmol) and triethylamine (400 μl), subsequently carrying out 1 day of stirring at room temperature. Triethylamine was evaporated, the resulting residue was mixed with 10% citric acid aqueous solution and then the thus precipitated material was collected by filtration and washed with water. This was dissolved in 80% water-containing ethanol (50 ml), mixed with triethylamine (5 ml) and then heated overnight under reflux. The solvent was evaporated, and the thus obtained residue was mixed with concentrated hydrochloric acid and stirred at room temperature for 15 minutes. The reaction solution was washed with chloroform and then, while cooling in an ice bath, alkalified with 50% sodium hydroxide aqueous solution. This was adjusted to pH 7.4 with concentrated hydrochloric acid, and the aqueous layer was extracted with chloroform (300 ml×3). The organic layer was dried over sodium sulfate, the solvent was evaporated, and the resulting residue was isolated and purified by a preparative TLC through its development with a lower layer of chloroform:methanol:water=7:3:1 and then recrystallized from 28% aqueous ammonia-ethanol to give 185 mg (47%) of the title compound in the form of light yellow crystals.

Provenance & Evidence