Toluene → Ethyl 1-cyclopropyl-6,7-difluoro-4-oxo-1,4-dihydroquinoline-3-carboxylate

HRID 1976830Notes

Reaction equation

HRID 1976830 reaction equation
C1(C)C=CC=CC=1.CN([C:11](=[CH2:17])[C:12]([O:14][CH2:15][CH3:16])=[O:13])C.F[C:19]1[CH:27]=[C:26]([F:28])[C:25]([F:29])=[CH:24][C:20]=1[C:21](Cl)=[O:22].[CH:30]1([NH2:33])[CH2:32][CH2:31]1>O.C(O)(=O)C.C(N(CC)CC)C>[CH:30]1([N:33]2[C:19]3[C:20](=[CH:24][C:25]([F:29])=[C:26]([F:28])[CH:27]=3)[C:21](=[O:22])[C:11]([C:12]([O:14][CH2:15][CH3:16])=[O:13])=[CH:17]2)[CH2:32][CH2:31]1

Participants

8

Reactant 4

HCID 1140TolueneHCID 69828CyclopropylamineHCID 1451642,4,5-Trifluorobenzoyl chlorideHCID 10103284HCID 10103284, compound

Product 1

HCID 9817544Ethyl 1-cyclopropyl-6,7-difluoro-4-oxo-1,4-dihydroquinoline-3-carboxylateYield 90.6%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 962WaterSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
55 °C

Procedure

272 g of toluene, 111 g of ethyl N,N-dimethylaminoacrylate and 85 g of triethylamine were initially charged, and 156 g of 2,4,5-trifluorobenzoyl chloride were added dropwise at from 50 to 55° C. over a period of 60 minutes. The mixture was subsequently stirred at 55° C. for 2 hours and then cooled to room temperature. 56 g of acetic acid were then added, and 48.6 g of cyclopropylamine were added dropwise at from 20 to 30° C. 250 ml of water were then added to the reaction mixture which was stirred for 15 minutes, and the organic phase was separated off. The organic phase was metered into a mixture of 65 g of potassium carbonate and 240 g of toluene, at 110° C. The water of reaction that was liberated was separated off via a water separator. After all the water had been separated off, the mixture was cooled to 30° C., and 500 ml of water were added. At a pressure of from 120 to 180 mbar, the toluene was distilled off. The mixture was subsequently cooled to 20° C. and the product was filtered off with suction. The isolated solid was washed three times with 100 ml of water each time and three times with 100 ml of isopropanol each time. Drying under reduced pressure at 50° C. gave 206 g of ethyl 1-cyclopropyl-6,7-difluoro-1,4-dihydro-4-oxo-3-quinoline-carboxylate. This corresponds to a yield of 88% of theory.

Workup

  1. temperaturecooled to room temperature
  2. stirringwas stirred for 15 minutes
  3. customthe organic phase was separated off
  4. additionThe organic phase was metered into a mixture of 65 g of potassium carbonate and 240 g of toluene, at 110° C
  5. customThe water of reaction that
  6. customwas liberated was separated off via a water separator
  7. customAfter all the water had been separated off
  8. temperaturethe mixture was cooled to 30° C.
  9. addition500 ml of water were added
  10. distillationAt a pressure of from 120 to 180 mbar, the toluene was distilled off
  11. temperatureThe mixture was subsequently cooled to 20° C.
  12. filtrationthe product was filtered off with suction
  13. washThe isolated solid was washed three times with 100 ml of water each time and three times with 100 ml of isopropanol each time
  14. customDrying under reduced pressure at 50° C.

Sources & evidence

ORD record
ord-8d89ba2a734f420f9fc1c26e77b570f6
Source dataset
uspto-grants-2001_05
Patent number
US06229017B1

Reaction notes

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