Biphenyl → 7-FLUORO-6-METHOXY-4-OXO-1,4-DIHYDROQUINOLINE-3-CARBONITRILE

HRID 1837329Notes

Reaction equation

HRID 1837329 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:6]=[CH:7][C:8]=1[O:9][CH3:10])[NH2:5].C([O:13][CH:14]=[C:15]([C:21]#[N:22])[C:16](OCC)=O)C.C1(OC2C=CC=CC=2)C=CC=CC=1.C1(C2C=CC=CC=2)C=CC=CC=1>C1(C)C=CC=CC=1.CCCCCC.C(OCC)(=O)C>[F:1][C:2]1[CH:3]=[C:4]2[C:6]([C:14](=[O:13])[C:15]([C:21]#[N:22])=[CH:16][NH:5]2)=[CH:7][C:8]=1[O:9][CH3:10]

Participants

8

Reactant 4

HCID 7095BiphenylHCID 7583Diphenyl EtherHCID 789432-Propenoic acid, 2-cyano-3-ethoxy-, ethyl esterHCID 5811103-Fluoro-4-methoxyaniline

Product 1

HCID 121507027-FLUORO-6-METHOXY-4-OXO-1,4-DIHYDROQUINOLINE-3-CARBONITRILEYield 2.6%

Reagents, catalysts & solvents 3

HCID 1140TolueneSolventHCID 8058HexaneSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
105 °C

Procedure

A mixture of 3-fluoro-4-methoxyaniline (15.31 g, 108 mmol) and ethyl (ethoxymethylene)cyanoacetate (18.36 g, 108 mmol) in toluene is heated at 100-110° C. for 4.5 hours then cooled to room temperature. A 1:1 mixture of hexane and ethyl acetate is added and the mixture is cooled on an ice bath. The solids are collected washing with hexane to provide a first crop of 26.10 g and a second crop of 1.24 g. A 2.0 g portion of this material is added to 18 mL of a 3:1 mixture of diphenyl ether:biphenyl that is heated to reflux. This mixture is heated at reflux for 4 hours then cooled and poured into hexane. The solids are collected by filtration and washed with ethyl acetate and hexane to provide 624 mg of 7-fluoro-6-methoxy-4-oxo-1,4,-dihydro-3-quinolinecarbonitrile as a brown solid. The filtrate is concentrated, the residue is dissolved in ethyl acetate and hexane is added. The resultant solid is collected by filtration to give 1.07 g of 7-fluoro-6-methoxy-4-oxo-1,4-dihydro-3-quinolinecarbonitrile as a yellow solid.

Workup

  1. temperaturethen cooled to room temperature
  2. additionis added
  3. temperaturethe mixture is cooled on an ice bath
  4. customThe solids are collected
  5. washwashing with hexane
  6. customto provide a first crop of 26.10 g
  7. temperatureThis mixture is heated
  8. temperatureat reflux for 4 hours
  9. temperaturethen cooled
  10. filtrationThe solids are collected by filtration
  11. washwashed with ethyl acetate and hexane

Sources & evidence

ORD record
ord-893fee5c2c06414f94fab4ce5a1ff024
Source dataset
uspto-grants-2004_08
Patent number
US06780996B2

Reaction notes

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