Water → 1-Cyclopropyl-8-difluoromethoxy-6-fluoro-7-(3-methylpiperazinyl)-1,4-dihydro-4-oxoquinoline-3-carboxylic acid

HRID 1440118Notes

Reaction equation

HRID 1440118 reaction equation
[CH3:1][CH:2]1[CH2:7][NH:6][CH2:5][CH2:4][NH:3]1.[B](F)F.[CH:11]1([N:14]2[C:23]3[C:18](=[CH:19][C:20]([F:29])=[C:21](F)[C:22]=3[O:24][CH:25]([F:27])[F:26])[C:17](=[O:30])[C:16]([C:31]([OH:33])=[O:32])=[CH:15]2)[CH2:13][CH2:12]1.O>CS(C)=O>[CH:11]1([N:14]2[C:23]3[C:18](=[CH:19][C:20]([F:29])=[C:21]([N:6]4[CH2:5][CH2:4][NH:3][CH:2]([CH3:1])[CH2:7]4)[C:22]=3[O:24][CH:25]([F:26])[F:27])[C:17](=[O:30])[C:16]([C:31]([OH:33])=[O:32])=[CH:15]2)[CH2:12][CH2:13]1

Participants

5

Reactant 3

HCID 962WaterHCID 660572-MethylpiperazineHCID 867452951-Cyclopropyl-8-difluoromethoxy-6,7-difluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acid boron difluoride

Product 1

HCID 150237881-Cyclopropyl-8-difluoromethoxy-6-fluoro-7-(3-methylpiperazinyl)-1,4-dihydro-4-oxoquinoline-3-carboxylic acidYield 82.2%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

1.63 g (0.016 moles) of 2-methylpiperazine was added to a solution of 2.58 g (0.0068 mole) of 1-cyclopropyl-8-difluoromethoxy-6,7-difluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acid boron difluoride chelate (prepared as described in Preparation 8) in 20 ml of dimethyl sulfoxide, and the mixture was allowed to stand at room temperature overnight. The reaction mixture was then poured into 100 ml of water, and the crystals which precipitated were collected by filtration and washed with water. The crystals were then dissolved in 500 ml of 80% v/v aqueous methanol containing 15 ml of triethylamine, and the solution was heated under reflux for 3 hours. At the end of this time, the solvent was removed by evaporation under reduced pressure, and the residue was washed with ethanol, to give 2.30 g of a pale yellow powder. The whole of this powder was dissolved in 50 ml of water, insoluble materials were removed by filtration, and the filtrate was adjusted to a pH value of 7.5 by the addition of a 1N aqueous solution of sodium hydroxide. The crystals which precipitated were collected by filtration and washed with water and with ethanol, in that order, to give 1.74 g of the title compound as fine pale yellow needles, melting at 223°-225° C.

Workup

  1. customthe crystals which precipitated
  2. filtrationwere collected by filtration
  3. washwashed with water
  4. dissolutionThe crystals were then dissolved in 500 ml of 80% v/v aqueous methanol containing 15 ml of triethylamine
  5. temperaturethe solution was heated
  6. temperatureunder reflux for 3 hours
  7. customAt the end of this time, the solvent was removed by evaporation under reduced pressure
  8. washthe residue was washed with ethanol

Sources & evidence

ORD record
ord-d7c02af022f84bc69c8c24e3d3c53aa6
Source dataset
uspto-grants-1996_03
Patent number
US05496951

Reaction notes

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