Water → Grepafloxacin

HRID 2271277Notes

Reaction equation

HRID 2271277 reaction equation
[CH:1]1([N:4]2[C:13]3[C:8](=[C:9]([CH3:16])[C:10]([F:15])=[C:11](F)[CH:12]=3)[C:7](=[O:17])[C:6]([C:18]([O:20]CC)=[O:19])=[CH:5]2)[CH2:3][CH2:2]1.[Cl-].[Li+].[CH3:25][CH:26]1[CH2:31][NH:30][CH2:29][CH2:28][NH:27]1.O>C(#N)C>[CH:1]1([N:4]2[C:13]3[C:8](=[C:9]([CH3:16])[C:10]([F:15])=[C:11]([N:30]4[CH2:29][CH2:28][NH:27][CH:26]([CH3:25])[CH2:31]4)[CH:12]=3)[C:7](=[O:17])[C:6]([C:18]([OH:20])=[O:19])=[CH:5]2)[CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 962WaterHCID 660572-MethylpiperazineHCID 433294Lithium ChlorideHCID 14651255Ethyl 1-cyclopropyl-6,7-difluoro-5-methyl-1,4-dihydro-4-oxoquinoline-3-carboxylate

Product 1

HCID 72474GrepafloxacinYield 97.3%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
100 °C

Procedure

To a suspension of 1.23 g of ethyl 1-cyclopropyl-6,7-difluoro-5-methyl-1,4-dihydro-4-oxoquinoline-3-carboxylate and 254 mg of lithium chloride in acetonitrile was added 1.00 g of 2-methylpiperazine, followed by heating and refluxing for 4 hours. After adding 24 ml of warm water, the reaction mixture was allowed to cool to precipitate crystals and the resulting crystals were filtered and washed with water. The crystals were suspended in 8 ml of isopropyl alcohol and 8 ml of 1N-NaOH, followed by stirring at a temperature in the range of 50° C. to 60° C. for 1 hour. After evaporating the isopropyl alcohol, to the residue were added 40 ml of water and 1.24 ml of concentrated hydrochloric acid, followed by washing with dichloromethane. The aqueous layer was heated at 100° C. for 1 hour to distill off the residual dichloromethane. After the aqueous layer was allowed to cool, 1.04 g of sodium hydrogencarbonate was added and heated with stirring at 60° C. for 1 hour, thereby neutralizing the aqueous layer. The aqueous layer was allowed to cool again, followed by stirring at 0° C. for 1 hour. The resulting crystals were filtered, washed with water and dried at 80° C. for 16 hours to give 1.40 g of 1-cyclopropyl-6-fluoro-7-(3-methyl-1-piperazinyl)-5-methyl-1,4-dihydro-4-oxoquinoline-3-carboxylic acid.

Workup

  1. temperatureby heating
  2. temperaturerefluxing for 4 hours
  3. temperatureto cool
  4. customto precipitate crystals
  5. filtrationthe resulting crystals were filtered
  6. washwashed with water
  7. customAfter evaporating the isopropyl alcohol
  8. additionto the residue were added 40 ml of water and 1.24 ml of concentrated hydrochloric acid
  9. washby washing with dichloromethane
  10. distillationto distill off the residual dichloromethane
  11. temperatureto cool
  12. addition1.04 g of sodium hydrogencarbonate was added
  13. temperatureheated
  14. stirringwith stirring at 60° C. for 1 hour
  15. temperatureto cool again
  16. stirringby stirring at 0° C. for 1 hour
  17. filtrationThe resulting crystals were filtered
  18. washwashed with water
  19. customdried at 80° C. for 16 hours

Sources & evidence

ORD record
ord-878866c2422045a4920e9340a5494c09
Source dataset
uspto-grants-2001_12
Patent number
US06333431B1

Reaction notes

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