Acetic Anhydride → 1-Cyclopropyl-6,7,8-trifluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid

HRID 2231410Notes

Reaction equation

HRID 2231410 reaction equation
F[C:2]1[C:7]([F:8])=[C:6]([F:9])[C:5]([F:10])=[CH:4][C:3]=1[C:11](=[O:18])[CH2:12][C:13]([O:15]CC)=[O:14].[CH2:19](OC(OCC)OCC)C.C(OC(=O)C)(=O)C.[CH:36]1([NH2:39])[CH2:38][CH2:37]1.CC(C)([O-])C.[K+]>C(O)(C)(C)C>[CH:36]1([N:39]2[C:2]3[C:3](=[CH:4][C:5]([F:10])=[C:6]([F:9])[C:7]=3[F:8])[C:11](=[O:18])[C:12]([C:13]([OH:15])=[O:14])=[CH:19]2)[CH2:38][CH2:37]1

Participants

7

Reactant 5

HCID 7918Acetic AnhydrideHCID 31214Ethyl orthoformateHCID 69828CyclopropylamineHCID 600916Ethyl 3-oxo-(2,3,4,5-tetrafluorophenyl)propanoateHCID 23665647Potassium tert-butoxide

Product 1

HCID 5354141-Cyclopropyl-6,7,8-trifluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acidYield 82%

Reagents, catalysts & solvents 1

HCID 6386tert-ButanolSolvent2×

Conditions

Temperature
120 °C

Procedure

To 17.6 g (66.6 mmol) of ethyl 2,3,4,5-tetrafluoro-β-oxobenzenepropanoate was added 14.6 g (~1.5 equivalents) of triethylorthoformate and 16.19 g (2.38 equivalents) of acetic anhydride. The mixture was refluxed for two hours at 120° C. (and was then cooled to 80° C. and concentrated in vacuo). The mixture was diluted with t-butanol, cooled to 10° C., and 3.8 g (1.05 equivalents) of cyclopropylamine in 120 ml of t-butanol was added. The mixture was stirred at 20° C. for 30 minutes and then warmed to 50° C. overnight. At this temperature 7.5 g of potassium t-butoxide was added in 50 ml of t-butanol and the mixture was stirred for four hours. It was filtered and the solids dissolved in 250 ml of hot acetic acid and 200 ml of 3N hydrochloric acid was added in portions over four hours at 100° C. The mixture was cooled and the solids collected to give 15.44 g (82%) of the 1-cyclopropyl-6,7,8-trifluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid; mp 226°-228° C.

Workup

  1. temperaturewas then cooled to 80° C.
  2. concentrationconcentrated in vacuo)
  3. additionThe mixture was diluted with t-butanol
  4. temperaturecooled to 10° C.
  5. temperaturewarmed to 50° C. overnight
  6. stirringthe mixture was stirred for four hours
  7. filtrationIt was filtered
  8. dissolutionthe solids dissolved in 250 ml of hot acetic acid
  9. addition200 ml of 3N hydrochloric acid was added in portions over four hours at 100° C
  10. temperatureThe mixture was cooled
  11. customthe solids collected

Sources & evidence

ORD record
ord-656bcb85bcb543cf8d2ae7a70d26ed9b
Source dataset
uspto-grants-1988_11
Patent number
US04782180

Reaction notes

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