Water → Vebufloxacin

HRID 1649449Notes

Reaction equation

HRID 1649449 reaction equation
[F:1][C:2]1[CH:14]=[C:12]2[C:13]3[N:8]([CH:9]=[C:10]([C:16]([OH:18])=[O:17])[C:11]2=[O:15])[CH:7]([CH3:19])[CH2:6][CH2:5][C:4]=3[C:3]=1Cl.[CH3:21][N:22]1[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]1.CN(C)P(=O)(N(C)C)N(C)C.O>C(O)(=O)C>[CH3:21][N:22]1[CH2:27][CH2:26][N:25]([C:3]2[C:4]3=[C:13]4[N:8]([CH:7]([CH3:19])[CH2:6][CH2:5]3)[CH:9]=[C:10]([C:16]([OH:18])=[O:17])[C:11](=[O:15])[C:12]4=[CH:14][C:2]=2[F:1])[CH2:24][CH2:23]1

Participants

6

Reactant 4

HCID 962WaterHCID 12679HexamethylphosphoramideHCID 531671-MethylpiperazineHCID 134729989-fluoro-8-chloro-5-methyl-6,7-dihydro-1-oxo-1H,5H-benzo[ij]quinolizine-2-carboxylic acid

Product 1

HCID 71235Vebufloxacin

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

A mixture of 1.8 g of 9-fluoro-8-chloro-5-methyl-6,7-dihydro-1-oxo-1H,5H-benzo[ij]quinolizine-2-carboxylic acid, 36 ml of N-methylpiperazine and 15 ml of hexamethylphosphoric triamide was heated at 150° to 160° C. for 4 hours. After completion of the reaction the solvent was removed by distillation under reduced pressure and the residue was washed with 10 ml of ethyl acetate. The crude crystals thus-obtained were mixed with 100 ml of water and adjusted to a pH of 4 with acetic acid. Insoluble materials were removed by filtration and the filtrate was treated with activated carbon followed by concentration under reduced pressure. The residue was mixed with 20 ml of water and the solution was adjusted to a pH of 9 with a 10% aqueous sodium hydroxide solution and extracted with 80 ml chloroform. After the extract was dried over anhydrous sodium sulfate and concentrated it was purified through a silica gel column chromatography (silica gel: Wako C-200, a trade name for a product of Wako Junyaku Co., Ltd.; eluent: chloroform-methanol (9:1 by volume)) to obtain 0.8 g of 8-(4-methyl-1-piperazinyl)-9-fluoro-5-methyl-6,7-dihydro-1-oxo-1H,5H-benzo[ij]quinolizine-2-carboxylic acid as white rhombic crystals having a melting point of 262° to 263° C.

Workup

  1. temperaturewas heated at 150° to 160° C. for 4 hours
  2. customAfter completion of the reaction the solvent
  3. customwas removed by distillation under reduced pressure
  4. washthe residue was washed with 10 ml of ethyl acetate
  5. customThe crude crystals thus-obtained
  6. customInsoluble materials were removed by filtration
  7. additionthe filtrate was treated with activated carbon
  8. concentrationfollowed by concentration under reduced pressure
  9. additionThe residue was mixed with 20 ml of water
  10. extractionextracted with 80 ml chloroform
  11. dry with materialAfter the extract was dried over anhydrous sodium sulfate
  12. concentrationconcentrated it
  13. customwas purified through a silica gel column chromatography (silica gel

Sources & evidence

ORD record
ord-54dc0033a30647d8a54a4ecaa5c2648d
Source dataset
uspto-grants-1983_11
Patent number
US04416884

Reaction notes

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