Diethyl [(3-chloro-4-fluoroanilino)methylidene]propanedioate → Ethyl 7-chloro-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylate

HRID 1607995Notes

Reaction equation

HRID 1607995 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][CH:10]=[C:11]([C:17]([O:19]CC)=O)[C:12]([O:14][CH2:15][CH3:16])=[O:13])[CH:5]=[CH:6][C:7]=1[F:8]>C1C=CC(C2C=CC=CC=2)=CC=1.C1C=CC(OC2C=CC=CC=2)=CC=1>[Cl:1][C:2]1[CH:3]=[C:4]2[C:5]([C:17](=[O:19])[C:11]([C:12]([O:14][CH2:15][CH3:16])=[O:13])=[CH:10][NH:9]2)=[CH:6][C:7]=1[F:8]

Participants

3

Reactant 1

HCID 533801Diethyl [(3-chloro-4-fluoroanilino)methylidene]propanedioate

Product 1

HCID 3018009Ethyl 7-chloro-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylateYield 89%

Reagents, catalysts & solvents 1

HCID 246701,1'-Biphenyl, mixt. with 1,1'-oxybis(benzene)Solvent2×

Conditions

Temperature
40 °C

Procedure

In a 30 gallon stainless steel unit, 55 L of Dowtherm A (a eutectic mixture of diphenyl and diphenyl ether) was stirred and heated at reflux (253°-257° C.) for one hour. To this was added a solution of 31.3 kg diethyl (3-chloro-4-fluorophenyl)aminomethylenepropanedioate in 10 L Dowtherm A held at 94°-98° C. The addition was effected over a period of four hours so that reflux of the reaction mixture was maintained. The reaction mixture was then allowed to cool and crystallization of the product began. After the temperature had reached 28°-30° C., the solid product was collected on a ceramic filter and washed with 2×9 L dimethylformamide (DMF). The damp filter cake was added to 65 L DMF in a 30 gallon kettle. The resulting slurry was heated at 90°-95° C. for 30 minutes and then cooled to 40° C. The solid was collected on a ceramic filter, washed with 2×8 L DMF and dried at 60° C. for 24 hours to give 23.8 kg ethyl 7-chloro-6-fluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylate containing about 10% of the 5-chloro-6-fluoro isomer as indicated by NMR spectra.

Workup

  1. temperatureheated
  2. temperatureat reflux (253°-257° C.) for one hour
  3. customheld at 94°-98° C
  4. additionThe addition
  5. temperatureso that reflux of the reaction mixture
  6. temperaturewas maintained
  7. temperatureto cool
  8. customcrystallization of the product
  9. customhad reached 28°-30° C.
  10. customthe solid product was collected on
  11. filtrationa ceramic filter
  12. washwashed with 2×9 L dimethylformamide (DMF)
  13. additionThe damp filter cake was added to 65 L DMF in a 30 gallon kettle
  14. temperatureThe resulting slurry was heated at 90°-95° C. for 30 minutes
  15. customThe solid was collected on a ceramic filter
  16. washwashed with 2×8 L DMF
  17. customdried at 60° C. for 24 hours

Sources & evidence

ORD record
ord-e6438658de6a4933957f1481d0d17a3a
Source dataset
uspto-grants-1989_09
Patent number
US04868305

Reaction notes

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