Dimethyl Sulfoxide → Gatifloxacin

HRID 492114Notes

Reaction equation

HRID 492114 reaction equation
CS(C)=O.[CH3:5][CH:6]1[CH2:11][NH:10][CH2:9][CH2:8][NH:7]1.[CH:12]1([N:15]2[C:24]3[C:19](=[CH:20][C:21]([F:28])=[C:22](F)[C:23]=3[O:25][CH3:26])[C:18](=[O:29])[C:17]([C:30]([OH:32])=[O:31])=[CH:16]2)[CH2:14][CH2:13]1>O>[CH3:5][CH:6]1[NH:7][CH2:8][CH2:9][N:10]([C:22]2[C:23]([O:25][CH3:26])=[C:24]3[N:15]([CH:12]4[CH2:13][CH2:14]4)[CH:16]=[C:17]([C:30]([OH:32])=[O:31])[C:18](=[O:29])[C:19]3=[CH:20][C:21]=2[F:28])[CH2:11]1

Participants

5

Reactant 3

HCID 679Dimethyl SulfoxideHCID 660572-MethylpiperazineHCID 70194651-Cyclopropyl-6,7-difluoro-1,4-dihydro-8-methoxy-4-oxo-3-quinolinecarboxylic acid

Product 1

HCID 5379GatifloxacinYield 104.2%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
48.5 °C

Procedure

A 100 L reactor was charged with DMSO (120 L) and 2-methylpiperazine (8.6 Kg) at 55° C. under nitrogen atmosphere. 1-cyclopropyl-6,7-difluoro-1,4 dihydro-8-methoxy-4-oxo-3-quinoline carboxylic acid (12 kg, divided in 4 portions of 3 kg each) of were added every 2 hours. After completion of the reaction (about 24 hours, monitoring by HPLC), the reaction mixture was cooled to about 47-50° C. and 24 L of water were added at this temperature. The resulting reaction mixture was cooled to 5° C. over 2 hours and maintained at this holding temperature for a holding time 18 hours. The resulting precipitate was collected by filtration to obtain 15.9 Kg of wet Gatifloxacin (11.6 Kg dry, 76% yield).

Workup

  1. customAfter completion of the reaction (about 24 hours, monitoring by HPLC)
  2. customThe resulting reaction mixture
  3. temperaturewas cooled to 5° C. over 2 hours
  4. temperaturemaintained at this holding temperature for a holding time 18 hours
  5. filtrationThe resulting precipitate was collected by filtration

Sources & evidence

ORD record
ord-71a88ccd52ba47b1b8cd4facdc59cef0
Source dataset
uspto-grants-2009_05
Patent number
US07531656B2

Reaction notes

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