Hydrochloric Acid → Ethyl 6,7-Difluoro-1-[(1R,2S)-2-fluorocyclopropyl]-5-methyl-4-oxo-1,4-dihydroquinoline-3-carboxylate

HRID 1939269Notes

Reaction equation

HRID 1939269 reaction equation
[F:1][C@H:2]1[CH2:4][C@H:3]1[NH:5][CH:6]=[C:7]([C:13](=[O:24])[C:14]1[C:19]([CH3:20])=[C:18]([F:21])[C:17]([F:22])=[CH:16][C:15]=1F)[C:8]([O:10][CH2:11][CH3:12])=[O:9].[H-].[Na+].Cl.ClCCl>O1CCOCC1.C(OCC)C>[F:21][C:18]1[C:19]([CH3:20])=[C:14]2[C:15](=[CH:16][C:17]=1[F:22])[N:5]([C@@H:3]1[CH2:4][C@@H:2]1[F:1])[CH:6]=[C:7]([C:8]([O:10][CH2:11][CH3:12])=[O:9])[C:13]2=[O:24]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 6344DichloromethaneHCID 24758Sodium hydrideHCID 178472047HCID 178472047, compound

Product 1

HCID 70250922Ethyl 6,7-Difluoro-1-[(1R,2S)-2-fluorocyclopropyl]-5-methyl-4-oxo-1,4-dihydroquinoline-3-carboxylateYield 77.8%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 312751,4-DioxaneSolvent

Procedure

In 25 ml of anhydrous dioxane was dissolved 2.40 g of ethyl 3-[(1R,2S)-2-fluorocyclopropylamino]-2-(2,4,5-trifluoro-6-methylbenzoyl)acrylate, and 338 mg of 60% sodium hydride in oil was added thereto under cooling with ice, followed by stirring at room temperature for 1 hour. The reaction mixture was poured into a mixture of 50 ml of 1N hydrochloric acid and 50 ml of dichloromethane, followed by stirring. The organic layer was separated. The aqueous layer was extracted with 100 ml of dichloromethane, and the extract was combined with the organic layer. The combined organic layer was dried over anhydrous sodium sulfate, the dichloromethane was removed by distillation, and the residue was dried in vacuo to yield yellow crude crystals. The crude crystals to yield with diethyl ether, filtered, and dried to yield 1.76 g of the titled compound as a pale yellow powder. The product was recrystallized from acetonitrile.

Workup

  1. additionwas added
  2. temperatureunder cooling with ice
  3. stirringby stirring
  4. customThe organic layer was separated
  5. extractionThe aqueous layer was extracted with 100 ml of dichloromethane
  6. dry with materialThe combined organic layer was dried over anhydrous sodium sulfate
  7. customthe dichloromethane was removed by distillation
  8. customthe residue was dried in vacuo
  9. customto yield yellow crude crystals
  10. filtrationfiltered
  11. customdried

Sources & evidence

ORD record
ord-d8da7f20b2d8401488b5960c4ffeabb9
Source dataset
uspto-grants-1997_12
Patent number
US05696132

Reaction notes

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