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

HRID 525966Notes

Reaction equation

HRID 525966 reaction equation
C[N:2]([CH3:21])[CH:3]=[C:4]([C:10](=[O:20])[C:11]1[CH:16]=[C:15]([F:17])[C:14]([F:18])=[CH:13][C:12]=1F)[C:5]([O:7][CH2:8][CH3:9])=[O:6].[CH2:22](OCC)[CH3:23].C1(N)CC1.C(=O)([O-])[O-].[K+].[K+]>C(O)C.O>[CH:21]1([N:2]2[C:12]3[C:11](=[CH:16][C:15]([F:17])=[C:14]([F:18])[CH:13]=3)[C:10](=[O:20])[C:4]([C:5]([O:7][CH2:8][CH3:9])=[O:6])=[CH:3]2)[CH2:23][CH2:22]1

Participants

7

Reactant 4

HCID 3283Diethyl EtherHCID 11430Potassium CarbonateHCID 69828CyclopropylamineHCID 53640509HCID 53640509, compound

Product 1

HCID 9817544Ethyl 1-cyclopropyl-6,7-difluoro-4-oxo-1,4-dihydroquinoline-3-carboxylateYield 97%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Procedure

A solution of ethyl 3-(dimethylamino)-2-(2,4,5-trifluorobenzoyl)acrylate (Example 48a) (75 g, 249 mmol) in a mixture of Ethanol (100 mL)/Diethyl ether (200 mL) was added to cyclopropanamine (34.5 mL, 498 mmol). After 2 h of stirring at rt, LCMS showed complete disappearance of starting material. The reaction mixture was evaporated under reduced pressure, the oily residue was dissolved in N,N-Dimethylformamide (DMF) (250 mL) and potassium carbonate (103 g, 747 mmol) was then added. The reaction mixture was stirred at 100° C. for 2 h, and LCMS showed completion of reaction. Cold water was added to the mixture. The precipitates were collected by filtration and dried to afford ethyl 1-cyclopropyl-6,7-difluoro-4-oxo-1,4-dihydroquinoline-3-carboxylate (71 g, 242 mmol, 97% yield) as a pale yellow solid. LCMS: [M+H]+: 294.1.

Workup

  1. customThe reaction mixture was evaporated under reduced pressure
  2. dissolutionthe oily residue was dissolved in N,N-Dimethylformamide (DMF) (250 mL)
  3. stirringThe reaction mixture was stirred at 100° C. for 2 h
  4. customcompletion of reaction
  5. filtrationThe precipitates were collected by filtration
  6. customdried

Sources & evidence

ORD record
ord-5f11eeaa34c141ac9ebedc3f88a16d6e
Source dataset
uspto-grants-2016_05
Patent number
US09340556B2

Reaction notes

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