Triethylamine → 7-([S,S]-2-t-Butoxycarbonyl-2,8-diazabicyclo[4.3.0]nonan-8-yl)-8-chloro-6-fluoro-1-[(1R,2S)-2-fluorocyclopropyl]-1,4-dihydro-4-oxoquinoline-3-carboxylic Acid

HRID 2256084Notes

Reaction equation

HRID 2256084 reaction equation
[Cl:1][C:2]1[C:3](F)=[C:4]([F:20])[CH:5]=[C:6]2[C:11]=1[N:10]([C@@H:12]1[CH2:14][C@@H:13]1[F:15])[CH:9]=[C:8]([C:16]([OH:18])=[O:17])[C:7]2=[O:19].[C:22]([O:26][C:27]([N:29]1[CH2:34][CH2:33][CH2:32][C@H:31]2[CH2:35][NH:36][CH2:37][C@@H:30]12)=[O:28])([CH3:25])([CH3:24])[CH3:23].C(N(CC)CC)C>C(#N)C>[C:22]([O:26][C:27]([N:29]1[CH2:34][CH2:33][CH2:32][C@@H:31]2[C@H:30]1[CH2:37][N:36]([C:3]1[C:2]([Cl:1])=[C:11]3[C:6]([C:7](=[O:19])[C:8]([C:16]([OH:18])=[O:17])=[CH:9][N:10]3[C@@H:12]3[CH2:14][C@@H:13]3[F:15])=[CH:5][C:4]=1[F:20])[CH2:35]2)=[O:28])([CH3:25])([CH3:23])[CH3:24]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 1519435(4aS,7aS)-tert-Butyl octahydro-1H-pyrrolo[3,4-b]pyridine-1-carboxylateHCID 104485478-Chloro-6,7-difluoro-1-((1R,2S)-2-fluorocyclopropyl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid

Product 1

HCID 699495847-([S,S]-2-t-Butoxycarbonyl-2,8-diazabicyclo[4.3.0]nonan-8-yl)-8-chloro-6-fluoro-1-[(1R,2S)-2-fluorocyclopropyl]-1,4-dihydro-4-oxoquinoline-3-carboxylic AcidYield 55.9%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

In 20 ml of acetonitrile were dissolved 344 mg of 8-chloro-6,7-difluoro-1-[(1R,2S)-2-fluorocyclopropyl]-1,4-dihydro-4-oxoquinoline-3-carboxylic acid, 490 mg of (S,S)-1-t-butoxycarbonyloctahydropyrrolo[3.4-b]pyridine (also termed "(S,S)-2-t-butoxycarbonyl-2,8-azabicyclo[4.3.0]nonane"), and 1 ml of triethylamine, and the solution was heated under reflux for 5 hours. After completion of the reaction, the solvent was removed under reduced pressure. To a residue was added 30 ml of water, followed by extracting with chloroform (30 ml×4). The combined organic layer was washed with 100 ml of a 10% citric acid aqueous solution and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure, and a residue was recrystallized from acetonitrile to yield 317 mg of the titled compound.

Workup

  1. temperaturethe solution was heated
  2. temperatureunder reflux for 5 hours
  3. customAfter completion of the reaction
  4. customthe solvent was removed under reduced pressure
  5. additionTo a residue was added 30 ml of water
  6. extractionby extracting with chloroform (30 ml×4)
  7. washThe combined organic layer was washed with 100 ml of a 10% citric acid aqueous solution
  8. dry with materialdried over anhydrous sodium sulfate
  9. customThe solvent was removed under reduced pressure
  10. customa residue was recrystallized from acetonitrile

Sources & evidence

ORD record
ord-829df0bd4686440da4905fdb17e5615f
Source dataset
uspto-grants-1997_08
Patent number
US05654318

Reaction notes

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