Sodium Hydroxide → 8-Chloro-7-[3,7-diazabicyclo[3.3.0]oct-1(5)-ene-3-yl]-6-fluoro-1-[(1R,2S)-2-fluorocyclopropyl]-1,4-dihydro-4-oxoquinoline-3-carboxylic acid

HRID 2256089Notes

Reaction equation

HRID 2256089 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].Br.Br.[C:24]12[CH2:31][NH:30][CH2:29][C:28]=1[CH2:27][NH:26][CH2:25]2.C1CCN2C(=NCCC2)CC1.[OH-].[Na+]>C(#N)C>[Cl:1][C:2]1[C:3]([N:26]2[CH2:27][C:28]3[CH2:29][NH:30][CH2:31][C:24]=3[CH2:25]2)=[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]

Participants

6

Reactant 4

HCID 14798Sodium HydroxideHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 104485478-Chloro-6,7-difluoro-1-((1R,2S)-2-fluorocyclopropyl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acidHCID 232828491,2,3,4,5,6-Hexahydropyrrolo[3,4-c]pyrrole dihydrobromide

Product 1

HCID 543611928-Chloro-7-[3,7-diazabicyclo[3.3.0]oct-1(5)-ene-3-yl]-6-fluoro-1-[(1R,2S)-2-fluorocyclopropyl]-1,4-dihydro-4-oxoquinoline-3-carboxylic acidYield 10.7%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A solution of 318 mg of 8-chloro-6,7-difluoro-1-[(1R,2S)-2-fluorocyclopropyl]-1,4-dihydro-4-oxoquinoline-3-carboxylic acid, 544 mg of 3,7-diazabicyclo[3.3.0]oct-1(5) -ene dihydrobromide (JP-A-3-193779) and 2 ml of DBU in 20 ml of acetonitrile was heated under reflux for 15 hours. To the mixture was added 1N sodium hydroxide, and an insoluble material was removed by filtration. To the filtrate, was added hydrochloric acid till pH became 7.4, and the mixture was extracted by five 50 ml portions of chloroform. A combined organic layer was dried over anhydrous sodium sulfate and the solvent was removed under reduced pressure. The residue was recrystallized from a mixture of ethanol and ammonia water to yield 43.7 mg of the titled compound.

Workup

  1. temperatureunder reflux for 15 hours
  2. customan insoluble material was removed by filtration
  3. additionTo the filtrate, was added hydrochloric acid
  4. extractionthe mixture was extracted by five 50 ml portions of chloroform
  5. dry with materialA combined organic layer was dried over anhydrous sodium sulfate
  6. customthe solvent was removed under reduced pressure
  7. customThe residue was recrystallized from a mixture of ethanol and ammonia water

Sources & evidence

ORD record
ord-182e778db8e14171b6fddad6184f080b
Source dataset
uspto-grants-1997_08
Patent number
US05654318

Reaction notes

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