Hydrochloric Acid → 6,7-difluoro-1,4-dihydro-1-[(1R,2S)-2-fluorocyclopropyl]-8-methoxy-4-oxo-3-quinolinecarboxylic acid

HRID 2183685Notes

Reaction equation

HRID 2183685 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:9](=[C:10]([O:13][CH3:14])[C:11]=1[F:12])[N:8]([C@@H:15]1[CH2:17][C@@H:16]1[F:18])[CH:7]=[C:6]([C:19]([O:21]CC)=[O:20])[C:5]2=[O:24].Cl>C(O)(=O)C>[F:1][C:2]1[CH:3]=[C:4]2[C:9](=[C:10]([O:13][CH3:14])[C:11]=1[F:12])[N:8]([C@@H:15]1[CH2:17][C@@H:16]1[F:18])[CH:7]=[C:6]([C:19]([OH:21])=[O:20])[C:5]2=[O:24]

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 60004315ethyl 6,7-difluoro-1-[(1R, 2S)-2-fluoro-1-cyclopropyl]-8-methoxy-1,4-dihydro-4-oxoquinoline-3-carboxylate

Product 1

HCID 120946186,7-difluoro-1,4-dihydro-1-[(1R,2S)-2-fluorocyclopropyl]-8-methoxy-4-oxo-3-quinolinecarboxylic acidYield 96.5%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

A mixture of ethyl 6,7-difluoro-1-[(1R, 2S)-2-fluoro-1-cyclopropyl]-8-methoxy-1,4-dihydro-4-oxoquinoline-3-carboxylate (120.8 g; 354.1 mmol), glacial acetic acid (210 ml), and conc. hydrochloric acid (420 ml) was refluxed for 6 hours, followed by cooling. The cooled reaction mixture was poured into ice/water (1500 ml) while being stirred, and the mixture was stirred for an additional 30 minutes at room temperature. Crystals precipitated were collected by filtration, and the crystals were sequentially washed with an excessive amount of purified water, ethanol (300 ml), and diethyl ether (500 ml). The crystals were purified through recrystallization from ethanol-acetone (also through treatment with activated carbon and filtration), followed by drying under reduced pressure at 70° C., to thereby yield 107.0 g of the title compound as white needles (yield: 96.5%).

Workup

  1. temperaturewas refluxed for 6 hours
  2. temperatureby cooling
  3. customThe cooled reaction mixture
  4. stirringthe mixture was stirred for an additional 30 minutes at room temperature
  5. customCrystals precipitated
  6. filtrationwere collected by filtration
  7. washthe crystals were sequentially washed with an excessive amount of purified water, ethanol (300 ml), and diethyl ether (500 ml)
  8. customThe crystals were purified through recrystallization from ethanol-acetone (also through treatment
  9. filtrationwith activated carbon and filtration),
  10. customby drying under reduced pressure at 70° C.

Sources & evidence

ORD record
ord-b8f7972cb7e046ff8f5315c029835cdb
Source dataset
uspto-grants-2005_05
Patent number
US06900225B2

Reaction notes

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