4-Fluoro-2-methylaniline → HCID 9997267, compound

HRID 1534484Notes

Reaction equation

HRID 1534484 reaction equation
[C:1]([C:6]1[CH:7]=[N:8][C:9]2[C:14]([C:15]=1Cl)=[CH:13][CH:12]=[CH:11][C:10]=2[O:17]C)(=[O:5])[CH2:2][CH2:3][CH3:4].[B].C(C1C=NC2C(C=1Cl)=CC=CC=2O)(=O)CCC.[F:37][C:38]1[CH:44]=[CH:43][C:41]([NH2:42])=[C:40]([CH3:45])[CH:39]=1>ClCCl.O1CCOCC1>[C:1]([C:6]1[CH:7]=[N:8][C:9]2[C:14]([C:15]=1[NH:42][C:41]1[CH:43]=[CH:44][C:38]([F:37])=[CH:39][C:40]=1[CH3:45])=[CH:13][CH:12]=[CH:11][C:10]=2[OH:17])(=[O:5])[CH2:2][CH2:3][CH3:4]

Participants

7

Reactant 4

HCID 679824-Fluoro-2-methylanilineHCID 5462311BoronHCID 10377396HCID 10377396, compoundHCID 117775673-Butyryl-4-chloro-8-methoxyquinoline

Product 1

HCID 9997267HCID 9997267, compoundYield 72.9%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Procedure

A solution of 3-butyryl-4-chloro-8-methoxyquinoline (131.9 g, 0.5 mol) in dichloromethane (1 liter), was cooled to -78° C., then boron tribomide (142 ml, 1.5 mol) added slowly over 10 minutes. The mixture was warmed slowly to 0°, stirred 2 hours, then allowed to warm to room temperature overnight. After recooling in ice the reaction was quenched cautiously with water, then the resulting solid filtered off and dried. This was heavily contaminated with boron-containing impurities, but was used without purification. Crude 3-butyryl-4-chloro-8-hydroxyquinoline (64 g) and 4-fluoro-2-methylaniline (16.7 ml, 0.15 mol) were dissolved in dioxan (300 ml), heated on a steam bath for 2 hours, then left to stand overnight. The dioxan was evaporated, dichloromethane and aqueous sodium bicarbonate added, the mixture stirred until all the solid had dissolved, then the organic layer dried and evaporated. Recrystallization from methanol gave 3-butyryl-4-(4-fluoro-2-methylphenylamino)-8-hydroxyquinoline (37 g) m.p. 121°-122°.

Workup

  1. temperatureThe mixture was warmed slowly to 0°
  2. customwas quenched cautiously with water
  3. filtrationthe resulting solid filtered off
  4. customdried
  5. additioncontaining impurities
  6. customwas used without purification
  7. temperatureheated on a steam bath for 2 hours
  8. waitleft
  9. waitto stand overnight
  10. customThe dioxan was evaporated
  11. additiondichloromethane and aqueous sodium bicarbonate added
  12. stirringthe mixture stirred until all the solid
  13. dissolutionhad dissolved
  14. customthe organic layer dried
  15. customevaporated
  16. customRecrystallization from methanol

Sources & evidence

ORD record
ord-8bc05fa98b69417685c49e2f08fb7b85
Source dataset
uspto-grants-1992_02
Patent number
US05089504

Reaction notes

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