Potassium Hydroxide → Brequinar

HRID 1086825Notes

Reaction equation

HRID 1086825 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6](=[O:11])[C:5]2=O.[CH3:13][CH2:14][C:15]([C:17]1[CH:22]=[CH:21][C:20]([C:23]2[C:28]([F:29])=[CH:27][CH:26]=[CH:25][CH:24]=2)=[CH:19][CH:18]=1)=O.[OH-:30].[K+]>C(O)C.O>[F:29][C:28]1[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=1[C:20]1[CH:21]=[CH:22][C:17]([C:15]2[C:14]([CH3:13])=[C:5]([C:6]([OH:11])=[O:30])[C:4]3[C:8](=[CH:9][CH:10]=[C:2]([F:1])[CH:3]=3)[N:7]=2)=[CH:18][CH:19]=1

Participants

6

Reactant 3

HCID 14797Potassium HydroxideHCID 2365665-FluoroisatinHCID 27374901-(2'-Fluoro[1,1'-biphenyl]-4-yl)propan-1-one

Product 1

HCID 57030BrequinarYield 50.9%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Procedure

5-Fluoroisatin (72.6 g, 0.44 mole) and 4-(2-fluorophenyl) propiophenone (100 g, 0.44 mole) were suspended in 720 ml of ethanol and stirred mechanically as a solution of KOH (147.8 g, 2.64 mole) in 300 ml of 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 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 precipitate was filtered, washed 2 times with 300 ml of ethyl ether and dried. Recrystallization from dimethylformamide and water gave 84 g of a white 2-(2'-Fluoro-1,1'-biphenyl-4-yl)-6-fluoro-3-methyl-4-quinolinecarboxylic acid, m.p. 315°-317°.

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 solid was dissolved in water
  7. washwashed with ethyl ether
  8. temperatureThe aqueous layer was cooled to 5°
  9. filtrationThe resulting precipitate was filtered
  10. washwashed 2 times with 300 ml of ethyl ether
  11. customdried
  12. customRecrystallization from dimethylformamide and water

Sources & evidence

ORD record
ord-39528f51957a493bb212e416a09d13a1
Source dataset
uspto-grants-1991_07
Patent number
US05032597

Reaction notes

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