Potassium Hydroxide → Brequinar Analog

HRID 1086824Notes

Reaction equation

HRID 1086824 reaction equation
[CH3:1][CH2:2][C:3]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[CH:7][CH:6]=1)=O.[F:17][C:18]1[CH:19]=[C:20]2[C:24](=[CH:25][CH:26]=1)[NH:23][C:22](=[O:27])[C:21]2=O.[OH-:29].[K+]>C(O)C.O>[C:8]1([C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=2)[CH:7]=[CH:6][C:5]([C:3]2[C:2]([CH3:1])=[C:21]([C:22]([OH:27])=[O:29])[C:20]3[C:24](=[CH:25][CH:26]=[C:18]([F:17])[CH:19]=3)[N:23]=2)=[CH:10][CH:9]=1

Participants

6

Reactant 3

HCID 14797Potassium HydroxideHCID 95230Propiophenone, 4'-phenyl-HCID 2365665-Fluoroisatin

Product 1

HCID 1543Brequinar AnalogYield 42.9%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Procedure

4-Phenylpropiophenone (18.9 g, 0.09 mole) and 5-fluoroisatin (20 g, 0.09 mole) were suspended in 360 ml of ethanol and stirred mechanically as a solution of 35.2 g KOH in 100 ml water was added dropwise over 15 minutes. The reaction mixture was heated at reflux for 12 hours, cooled, and the ethanol evaporated under reduced pressure. The resulting yellow solid was dissolved in water and washed with ethyl ether. The aqueous layer was cooled to 5° and acidified with glacial acetic acid. The resulting yellow precipitate was filtered and dried. Recrystallization from 200 ml of dimethylformamide and 25 ml water provided 13.8 g of 2-(4-biphenylyl)-6-fluoro-3-methylquinoline-4-carboxylic acid as a white solid, m.p. 303°-306° (d).

Workup

  1. additionwas added dropwise over 15 minutes
  2. temperatureThe reaction mixture was heated
  3. temperatureat reflux for 12 hours
  4. temperaturecooled
  5. customthe ethanol evaporated under reduced pressure
  6. dissolutionThe resulting yellow solid was dissolved in water
  7. washwashed with ethyl ether
  8. temperatureThe aqueous layer was cooled to 5°
  9. filtrationThe resulting yellow precipitate was filtered
  10. customdried
  11. customRecrystallization from 200 ml of dimethylformamide and 25 ml water

Sources & evidence

ORD record
ord-39e8c1b76a344f46965b0b8d11cf45ec
Source dataset
uspto-grants-1991_07
Patent number
US05032597

Reaction notes

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