Hydrochloric Acid → Moxifloxacin hydrochloride

HRID 873244Notes

Reaction equation

HRID 873244 reaction equation
[CH3:1][O:2][C:3]1[C:8]([N:9]2[CH2:17][C@@H:16]3[C@@H:11]([CH2:12][CH2:13][CH2:14][NH:15]3)[CH2:10]2)=[C:7]([F:18])[CH:6]=[C:5]2[C:19]([C:21]([C:27]([OH:29])=[O:28])=[CH:22][N:23]([CH:24]3[CH2:26][CH2:25]3)[C:4]=12)=[O:20].S(C1C=CC(C)=CC=1)([O-])(=O)=O.C([O-])(O)=O.[Na+].O.[ClH:47]>C(O)C.C(O)(C)C.ClCCl>[CH3:1][O:2][C:3]1[C:8]([N:9]2[CH2:17][C@@H:16]3[C@@H:11]([CH2:12][CH2:13][CH2:14][NH:15]3)[CH2:10]2)=[C:7]([F:18])[CH:6]=[C:5]2[C:19]([C:21]([C:27]([OH:29])=[O:28])=[CH:22][N:23]([CH:24]3[CH2:26][CH2:25]3)[C:4]=12)=[O:20].[ClH:47]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 516892Sodium BicarbonateHCID 86677579HCID 86677579, compound

Product 1

HCID 101526Moxifloxacin hydrochlorideYield 10.1%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 3776IsopropanolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

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.

Workup

  1. customprovided with a mechanical stirrer
  2. temperatureHeating
  3. customwas carried out at 30-35° C.
  4. dissolutiondissolution
  5. customThen the phases were separated
  6. extractionthe aqueous phase was extracted
  7. customThe organic phases were collected
  8. customdried
  9. customThe obtained solid was recovered with 954.8 mL of Ethanol and 136.4 mL of purified water
  10. temperatureHeating
  11. temperatureat reflux up
  12. dissolutiondissolution
  13. customwas brought to 60° C.
  14. waitto r.t in 4 hours
  15. waitit was left at room temperature for at least 4 hours
  16. waitit was left at 0° C. for another 4 hours
  17. filtrationThe obtained crystal was filtered
  18. washwashing it with 68.2 mL of Ethanol
  19. customThe obtained salt was dried at 50° C. under vacuum for 24 hours

Sources & evidence

ORD record
ord-84a5269495dd4bbf994c383f93b7d903
Source dataset
uspto-grants-2015_03
Patent number
US08975408B2

Reaction notes

Loading…