Water → Ethyl 7-fluoro-1-[2-(S)-fluoro-1-(R)-cyclopropyl]-1,4-dihydro-8-methoxy-5-nitro-4-oxoquinoline-3-carboxylate

HRID 600874Notes

Reaction equation

HRID 600874 reaction equation
N(OCCC(C)C)=O.N[C:10]1[C:11]([N+:33]([O-:35])=[O:34])=[C:12]2[C:17](=[C:18]([O:21][CH3:22])[C:19]=1[F:20])[N:16]([C@@H:23]1[CH2:25][C@@H:24]1[F:26])[CH:15]=[C:14]([C:27]([O:29][CH2:30][CH3:31])=[O:28])[C:13]2=[O:32].O>CN(C)C=O>[F:20][C:19]1[C:18]([O:21][CH3:22])=[C:17]2[C:12]([C:13](=[O:32])[C:14]([C:27]([O:29][CH2:30][CH3:31])=[O:28])=[CH:15][N:16]2[C@@H:23]2[CH2:25][C@@H:24]2[F:26])=[C:11]([N+:33]([O-:35])=[O:34])[CH:10]=1

Participants

5

Reactant 3

HCID 962WaterHCID 8053Isoamyl NitriteHCID 67271603Ethyl 6-amino-7-fluoro-1-[2-(S)-fluoro-1-(R)-cyclopropyl]-1,4-dihydro-8-methoxy-5-nitro-4-oxoquinoline-3-carboxylate

Product 1

HCID 67272210Ethyl 7-fluoro-1-[2-(S)-fluoro-1-(R)-cyclopropyl]-1,4-dihydro-8-methoxy-5-nitro-4-oxoquinoline-3-carboxylateYield 45%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
70 °C

Procedure

Isoamyl nitrite (3.81 g, 32.5 mmol) was added to dimethylformamide (60 ml), and while stirring at 70° C., a solution, wherein ethyl 6-amino-7-fluoro-1-[2-(S)-fluoro-1-(R)-cyclopropyl]-1,4-dihydro-8-methoxy-5-nitro-4-oxoquinoline-3-carboxylate (8.90 g, 23.2 mmol) was dissolved in dimethylformamide (120 ml), was added dropwise thereto over a period of 3 hours. After completion of dripping, the reaction solution was stirred at 70° C. for 1 hour, allowed to cool, and then poured into water (500 ml). After extraction with ethyl acetate (300 ml×3), the organic layers combined were washed with 1 mol/l hydrochloric acid (300 ml) and saturated saline solution (200 ml×2) in that order, and then dried over anhydrous sodium sulfate. After filtering, the filtrate was concentrated under a reduced pressure, and the crude crystals obtained were recrystallized in ethanol and then dried under a reduced pressure. 3.81 g (45%) of the title compound was thereby obtained in the form of yellow crystals.

Workup

  1. additionwas added dropwise
  2. stirringthe reaction solution was stirred at 70° C. for 1 hour
  3. temperatureto cool
  4. extractionAfter extraction with ethyl acetate (300 ml×3)
  5. washthe organic layers combined were washed with 1 mol/l hydrochloric acid (300 ml) and saturated saline solution (200 ml×2) in that order
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationAfter filtering
  8. concentrationthe filtrate was concentrated under a reduced pressure
  9. customthe crude crystals obtained
  10. customwere recrystallized in ethanol
  11. customdried under a reduced pressure

Sources & evidence

ORD record
ord-b84d1a7cbc2a43dbae707732fe806e5f
Source dataset
uspto-grants-2011_03
Patent number
US07902226B2

Reaction notes

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