Acetic Anhydride → Ethyl 1-cyclopropyl-6,7,8-trifluoro-5-nitro-4-oxo-1,4-dihydroquinoline-3-carboxylate

HRID 620878Notes

Reaction equation

HRID 620878 reaction equation
[N+:1]([C:4]1[C:9]([F:10])=[C:8]([F:11])[C:7]([F:12])=[C:6](F)[C:5]=1[C:14](=[O:21])[CH2:15][C:16]([O:18][CH2:19][CH3:20])=[O:17])([O-:3])=[O:2].[CH2:22](OC(OCC)OCC)C.C(OC(=O)C)(=O)C.[CH:39]1([NH2:42])[CH2:41][CH2:40]1.CC(C)([O-])C.[K+]>C(O)(C)(C)C>[CH:39]1([N:42]2[C:6]3[C:5](=[C:4]([N+:1]([O-:3])=[O:2])[C:9]([F:10])=[C:8]([F:11])[C:7]=3[F:12])[C:14](=[O:21])[C:15]([C:16]([O:18][CH2:19][CH3:20])=[O:17])=[CH:22]2)[CH2:41][CH2:40]1

Participants

7

Reactant 5

HCID 7918Acetic AnhydrideHCID 31214Ethyl orthoformateHCID 69828CyclopropylamineHCID 140068562-Nitro-3,4,5,6-tetrafluoro-beta-oxobenzenepropanoic acid, ethyl esterHCID 23665647Potassium tert-butoxide

Product 1

HCID 14006857Ethyl 1-cyclopropyl-6,7,8-trifluoro-5-nitro-4-oxo-1,4-dihydroquinoline-3-carboxylateYield 24.2%

Reagents, catalysts & solvents 1

HCID 6386tert-ButanolSolvent

Conditions

Temperature
45 °C

Procedure

A solution of 6.8 g (22 mmoles) of 2-nitro-3,4,5,6-tetrafluoro-β-oxobenzenepropanoic acid, ethyl ester, 4.9 g (33 mmoles) of triethylorthoformate and 50 ml of acetic anhydride was heated at reflux for two hours. The solvent was removed in vacuo and then in high vacuo at 80° C. for 1.5 hours. The residue was dissolved in 25 ml of t-butanol and treated with 1.43 g (25 mmoles) of cyclopropylamine. The mixture was heated at 45° C. for four hours, cooled to room temperature and treated dropwise with a solution of 2.47 g (25 mmoles) of potassium t-butoxide in 25 ml of t-butanol. The reaction was heated at 60° C. for six hours and the solvent was removed in vacuo. The residue was dissolved in chloroform, washed with water, dried (MgSO4), and evaporated in vacuo. The residue was chromatographed over silica gel eluting with chloroform/ethyl acetate (80/20) to give 1.9 g of the title compound as an oil which was used without further purification.

Workup

  1. temperatureat reflux for two hours
  2. customThe solvent was removed in vacuo
  3. dissolutionThe residue was dissolved in 25 ml of t-butanol
  4. temperaturecooled to room temperature
  5. temperatureThe reaction was heated at 60° C. for six hours
  6. customthe solvent was removed in vacuo
  7. dissolutionThe residue was dissolved in chloroform
  8. washwashed with water
  9. dry with materialdried (MgSO4)
  10. customevaporated in vacuo
  11. customThe residue was chromatographed over silica gel eluting with chloroform/ethyl acetate (80/20)

Sources & evidence

ORD record
ord-92734f72dc9a4ee287dd961f717a8e2a
Source dataset
uspto-grants-1989_04
Patent number
US04822801

Reaction notes

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