Dimethyl Sulfoxide → Levofloxacin Hydrate

HRID 1866748

Reaction equation

HRID 1866748 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.CS(C)=[O:23].[CH3:25][N:26]1[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]1.C(O)(C)C>O>[CH3:10][C@@H:7]1[N:6]2[CH:11]=[C:12]([C:17]([OH:19])=[O:18])[C:13]([C:14]3=[CH:15][C:2]([F:1])=[C:3]([N:29]4[CH2:30][CH2:31][N:26]([CH3:25])[CH2:27][CH2:28]4)[C:4](=[C:5]23)[O:9][CH2:8]1)=[O:16].[CH3:10][C@@H:7]1[N:6]2[CH:11]=[C:12]([C:17]([OH:19])=[O:18])[C:13]([C:14]3=[CH:15][C:2]([F:1])=[C:3]([N:29]4[CH2:30][CH2:31][N:26]([CH3:25])[CH2:27][CH2:28]4)[C:4](=[C:5]23)[O:9][CH2:8]1)=[O:16].[OH2:23]

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 3776IsopropanolHCID 531671-MethylpiperazineHCID 688333Levofloxacin q-acid

Product 1

HCID 3033924Levofloxacin Hydrate

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

In 1 liter reactor equipped with a mechanical stirrer, a condenser and a thermometer, heated at 80° C., was charged 87.5 g (0.31 mole) of (S)-(−)-9,10-difluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carboxylic acid, 61.3 mL DMSO and 86.3 mL (0.77 mole) of N-methylpiperazine. The slurry was stirred at a rate of 250 rpm under nitrogen atmosphere at 80° C. until completion of the reaction (monitoring by HPLC). Then the slurry was cooled to 75° C. and a mixture of isopropanol (675 mL) and water (25 mL) was added dropwise at this temperature during 2 hours. The slurry was then cooled to 5° C. during 4 hours, maintained at this temperature for 2 hours and filtrated under vacuum at this temperature. The solid was then washed with 175 mL of isopropanol (2 rinses) and dried under vacuum to obtain levofloxacin hemihydrate.

Workup

  1. customIn 1 liter reactor equipped with a mechanical stirrer, a condenser
  2. temperatureThen the slurry was cooled to 75° C.
  3. additionwas added dropwise at this temperature during 2 hours
  4. temperatureThe slurry was then cooled to 5° C. during 4 hours
  5. temperaturemaintained at this temperature for 2 hours
  6. filtrationfiltrated under vacuum at this temperature
  7. washThe solid was then washed with 175 mL of isopropanol (2 rinses)
  8. customdried under vacuum

Sources & evidence

ORD record
ord-d1a4b4f3d4e44f96a2f782490ba6d320
Source dataset
uspto-grants-2009_12
Patent number
US07629458B2

Linked notes

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