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

HRID 600869Notes

Reaction equation

HRID 600869 reaction equation
N(OCCC(C)C)=O.N[C:10]1[C:11]([N+:32]([O-:34])=[O:33])=[C:12]2[C:17](=[C:18]([CH3:21])[C:19]=1[F:20])[N:16]([C@@H:22]1[CH2:24][C@@H:23]1[F:25])[CH:15]=[C:14]([C:26]([O:28][CH2:29][CH3:30])=[O:27])[C:13]2=[O:31].O.C(Cl)(Cl)Cl>CN(C)C=O>[F:20][C:19]1[C:18]([CH3:21])=[C:17]2[C:12]([C:13](=[O:31])[C:14]([C:26]([O:28][CH2:29][CH3:30])=[O:27])=[CH:15][N:16]2[C@@H:22]2[CH2:24][C@@H:23]2[F:25])=[C:11]([N+:32]([O-:34])=[O:33])[CH:10]=1

Participants

6

Reactant 4

HCID 962WaterHCID 6212ChloroformHCID 8053Isoamyl NitriteHCID 67271091ethyl 6-amino-7-fluoro-1-[2-(S)-fluoro-1-(R)-cyclopropyl]-1,4-dihydro-8-methyl-5-nitro-4-oxoquinoline-3-carboxylate

Product 1

HCID 67272057Ethyl 7-fluoro-1-[2-(S)-fluoro-1-(R)-cyclopropyl]-1,4-dihydro-8-methyl-5-nitro-4-oxoquinoline-3-carboxylateYield 61%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
65 °C

Procedure

Isoamyl nitrite (2.56 ml, 19.1 mmol) was added to dimethylformamide (40 ml), and while stirring at 65° C., a solution, wherein ethyl 6-amino-7-fluoro-1-[2-(S)-fluoro-1-(R)-cyclopropyl]-1,4-dihydro-8-methyl-5-nitro-4-oxoquinoline-3-carboxylate (5.00 g, 13.6 mmol) was dissolved in dimethylformamide (60 ml), was added dropwise over a period of 3 hours. After completion of dripping, the reaction solution was stirred at 65° C. for 4 hours, allowed to cool, and then poured into water (500 ml). After extraction with chloroform (200 ml×3), the organic layers combined were washed with 1 mol/l hydrochloric acid (200 ml) and saturated saline solution (100 ml×2) in that order, and then dried over anhydrous sodium sulfate. After filtering, the filtrate was concentrated under a reduced pressure, and the residue obtained was applied to a silica gel chromatography to obtain 2.91 g (61%) of the title compound in the form of a white powder from a chloroform:methanol=30:1 eluate.

Workup

  1. additionwas added dropwise over a period of 3 hours
  2. stirringthe reaction solution was stirred at 65° C. for 4 hours
  3. temperatureto cool
  4. extractionAfter extraction with chloroform (200 ml×3)
  5. washthe organic layers combined were washed with 1 mol/l hydrochloric acid (200 ml) and saturated saline solution (100 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 residue obtained

Sources & evidence

ORD record
ord-df8acdd37605477fbd79c33b9249582f
Source dataset
uspto-grants-2011_03
Patent number
US07902226B2

Reaction notes

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