1-Methylpiperazine → Levofloxacin

HRID 1866745Notes

Reaction equation

HRID 1866745 reaction equation
[F:1][C:2]1[C:3](F)=[C:4]2[O:9][CH2:8][C@H:7]([CH3:10])[N:6]3[CH:11]=[C:12]([C:17]([OH:19])=[O:18])[C:13](=[O:16])[C:14]([CH:15]=1)=[C:5]23.[CH3:21][N:22]1[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]1>C(O)C(C)C>[CH3:10][C@@H:7]1[N:6]2[C:5]3[C:14]([C:13]([C:12]([C:17]([OH:19])=[O:18])=[CH:11]2)=[O:16])=[CH:15][C:2]([F:1])=[C:3]([N:25]2[CH2:26][CH2:27][N:22]([CH3:21])[CH2:23][CH2:24]2)[C:4]=3[O:9][CH2:8]1

Participants

4

Reactant 2

HCID 531671-MethylpiperazineHCID 688333Levofloxacin q-acid

Product 1

HCID 149096LevofloxacinYield 77.3%

Reagents, catalysts & solvents 1

HCID 6560IsobutanolSolvent

Conditions

Temperature
0 °C

Procedure

3 g (10.67 mmole) of (S)-(−)-9,10-difluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyrido [1,2,3-de] [1,4]benzoxazine-6-carboxylic acid was put in suspension in 21 mL of isobutanol and 4.75 mL (43 mmole) of N-methyl piperazine. The reaction mixture was heated to reflux for 6 hours, then slurried at ambient temperature for 60 hours and heated again to reflux for 7 hours until completion of the reaction. During that time, the reaction mixture became soluble at reflux temperature. The mixture was then cooled to 0° C., filtered under vacuum, washed with 7 mL isobutanol and 10 mL n-heptane, and dried overnight to obtain 2.83 g (77.3%) of levofloxacin.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux for 6 hours
  3. temperatureheated again
  4. temperatureto reflux for 7 hours until completion of the reaction
  5. temperatureat reflux temperature
  6. filtrationfiltered under vacuum
  7. washwashed with 7 mL isobutanol and 10 mL n-heptane
  8. customdried overnight

Sources & evidence

ORD record
ord-4ef587116a3a4c53b425d75c7f1018b3
Source dataset
uspto-grants-2009_12
Patent number
US07629458B2

Reaction notes

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