Water → 7-[(S,S)-2,8-diazabicyclo[4.3.0]nonan-8-yl]-6,8-difluoro-1-[(1R,2S)-2-fluorocyclopropyl]-1,4-dihydro-4-oxoquinoline-3-carboxylic acid

HRID 2256085Notes

Reaction equation

HRID 2256085 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:9](=[C:10]([F:13])[C:11]=1F)[N:8]([C@@H:14]1[CH2:16][C@@H:15]1[F:17])[CH:7]=[C:6]([C:18]([OH:20])=[O:19])[C:5]2=[O:21].[C@@H:22]12[CH2:30][NH:29][CH2:28][C@@H:27]1[CH2:26][CH2:25][CH2:24][NH:23]2.C(N(CC)CC)C.O>C(#N)C>[C@@H:22]12[CH2:30][N:29]([C:11]3[C:10]([F:13])=[C:9]4[C:4]([C:5](=[O:21])[C:6]([C:18]([OH:20])=[O:19])=[CH:7][N:8]4[C@@H:14]4[CH2:16][C@@H:15]4[F:17])=[CH:3][C:2]=3[F:1])[CH2:28][C@@H:27]1[CH2:26][CH2:25][CH2:24][NH:23]2

Participants

6

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 10313138(1S,6S)-2,8-Diazabicyclo(4.3.0)nonaneHCID 229583606,7,8-trifluoro-1-[(1R,2S)-2-fluorocyclopropyl]-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid

Product 1

HCID 545391447-[(S,S)-2,8-diazabicyclo[4.3.0]nonan-8-yl]-6,8-difluoro-1-[(1R,2S)-2-fluorocyclopropyl]-1,4-dihydro-4-oxoquinoline-3-carboxylic acidYield 78.6%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A solution of 301 mg of 6,7,8-trifluoro-1-[(1R,2S)-2-fluorocyclopropyl]-1,4-dihydro-4-oxoquinoline-3-carboxylic acid (JP-A-5-163244), 463 mg of (S,S)-2,8-diazabicyclo[4.3.0]nonane, 1 ml of triethylamine in 10 ml of acetonitrile was heated under reflux for 15 hours. To the mixture was added 50 ml of water, and the solvent was removed under reduced pressure. The mixture was extracted from three 50 ml portions of chloroform, and the extract was dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure. A residue was dissolved in 10 ml of trifluoroacetic acid, and the solution was stirred at room temperature for 2 hours. Trifluoracetic acid was removed under reduced pressure and to a residue was added 1N sodium hydroxide aqueous solution till a pH became 12. To the solution was added hydrochloric acid till the pH became 7.4. The solution was extracted with six 50 ml portions of chloroform. The extract was dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure and a residue was recrystallized from ethanol to yield 320 mg of the titled compound.

Workup

  1. temperatureunder reflux for 15 hours
  2. customthe solvent was removed under reduced pressure
  3. extractionThe mixture was extracted from three 50 ml portions of chloroform
  4. dry with materialthe extract was dried over anhydrous sodium sulfate
  5. customThe solvent was removed under reduced pressure
  6. dissolutionA residue was dissolved in 10 ml of trifluoroacetic acid
  7. customTrifluoracetic acid was removed under reduced pressure and to a residue
  8. additionwas added 1N sodium hydroxide aqueous solution till a pH
  9. additionTo the solution was added hydrochloric acid till the pH
  10. extractionThe solution was extracted with six 50 ml portions of chloroform
  11. dry with materialThe extract was dried over anhydrous sodium sulfate
  12. customThe solvent was removed under reduced pressure
  13. customa residue was recrystallized from ethanol

Sources & evidence

ORD record
ord-f4a4ec3cd6c14fd9a5263fe20b1679fc
Source dataset
uspto-grants-1997_08
Patent number
US05654318

Reaction notes

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