Hydrochloric Acid → Moxifloxacin hydrochloride

Participants

Reaction Conditions

Reaction Steps

68.2 g of purified moxifloxacin tosylate of example 2 (1.0 mol. Equiv.) (HPLC purity equivalent to 99.30% and impurity of formula (VII) equivalent to 0.27%), 409.2 mL of saturated NaHCO3 solution, 136.4 mL of purified water, 409.2 mL of dichloromethane and 68.2 mL of isopropanol were introduced into a 4-neck flask provided with a mechanical stirrer, thermometer, cooler and thermostat. Heating was carried out at 30-35° C. and stirring was carried out for one hour up to complete dissolution. Then the phases were separated and the aqueous phase was extracted using 136.4 mL of Dichloromethane. The organic phases were collected and dried. The obtained solid was recovered with 954.8 mL of Ethanol and 136.4 mL of purified water. Heating was carried out at reflux up to complete dissolution, then it was brought to 60° C. and a solution of 12.3 mL of concentrated hydrochloric acid (32%) (1.05 mol. equiv.) and 136.4 mL of Ethanol was dripped in 2 hours. It was brought to r.t in 4 hours, it was left at room temperature for at least 4 hours, then it was cooled at 0° C. and it was left at 0° C. for another 4 hours. The obtained crystal was filtered washing it with 68.2 mL of Ethanol. The obtained salt was dried at 50° C. under vacuum for 24 hours. 44.3 g of moxifloxacin hydrochloride with a molar yield equivalent to 85.1% with HPLC purity equivalent to 99.79% and a formula (VII) impurity content equivalent to 0.08% was obtained. The obtained product does not contain, even at ppm level, any ester of sulfonic acids as an impurity. This is important because it is well-known that such impurities are genotoxic.

Provenance & Evidence