Reaktion #2358459

Reaktionsgleichung

water

ethyl 1-cyclopropyl-6,7-difluoro-5-methyl-1,4-dihydro-4-oxoquinoline-3-carboxylate

lithium chloride

2-methylpiperazine

→

1-cyclopropyl-6-fluoro-7-(3-methyl-1-piperazinyl)-5-methyl-1,4-dihydro-4-oxoquinoline-3-carboxylic acid

Ausbeute 97.3%

Lösungsmittel

acetonitrile

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturby heating
2. 2
   Temperaturrefluxing for 4 hours
3. 3
   Temperaturto cool
4. 4
   Sonstigeto precipitate crystals
5. 5
   Filtrationthe resulting crystals were filtered
6. 6
   Waschenwashed with water
7. 7
   SonstigeAfter evaporating the isopropyl alcohol
8. 8
   workup.ADDITIONto the residue were added 40 ml of water and 1.24 ml of concentrated hydrochloric acid
9. 9
   Waschenby washing with dichloromethane
10. 10
    workup.DISTILLATIONto distill off the residual dichloromethane
11. 11
    Temperaturto cool
12. 12
    workup.ADDITION1.04 g of sodium hydrogencarbonate was added
13. 13
    Temperaturheated
14. 14
    workup.STIRRINGwith stirring at 60° C. for 1 hour
15. 15
    Temperaturto cool again
16. 16
    workup.STIRRINGby stirring at 0° C. for 1 hour
17. 17
    FiltrationThe resulting crystals were filtered
18. 18
    Waschenwashed with water
19. 19
    Sonstigedried at 80° C. for 16 hours

Vorschrift

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.

Quelle