Hydrochloric Acid → 8-Bromo-6-fluoro-5-methoxy-2-methylquinoline

HRID 495438Notes

Reaction equation

HRID 495438 reaction equation
[Br:1][C:2]1[C:7]([NH2:8])=[CH:6][C:5]([O:9][CH3:10])=[C:4]([F:11])[CH:3]=1.Cl.[C:13]1(Cl)[C:19](=O)C(Cl)=C(Cl)[C:15](=O)[C:14]=1Cl.C(=O)/C=C/C.[OH-].[Na+]>O>[Br:1][C:2]1[CH:3]=[C:4]([F:11])[C:5]([O:9][CH3:10])=[C:6]2[C:7]=1[N:8]=[C:14]([CH3:15])[CH:13]=[CH:19]2

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 8371ChloranilHCID 14798Sodium HydroxideHCID 447466CrotonaldehydeHCID 223266662-Bromo-4-fluoro-5-methoxyaniline

Product 1

HCID 223267328-Bromo-6-fluoro-5-methoxy-2-methylquinolineYield 34.4%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To 6-bromo-4-fluoro-3-methoxyaniline (7.0 g, 32 mmol) was added conc. HCl (10 ml) followed by p-chloranil (7.80 g, 32 mmol), then nbutanol (10 ml) was added and the whole mix heated up to reflux, with stirring. A solution of crotonaldehyde (2.7 g 38.4 mmol) in nbutanol (5 ml), was added slowly over 0.5 h, and reflux continued for a further 0.5 h. The reaction mixture was allowed to cool, and the basified to pH14 using 50% NaOH solution. The reaction mixture was diluted with water (200 ml) and extracted with dichloromethane (3×100 ml). The combined organic extracts were dried over Na2SO4 and evaporated in vacuo to give a dark oil which was chromatographed on silica gel (˜200 g) eluting from 20% ethyl acetate in hexane to give the title compound as a brown oil (2.97 g, 34%).

Workup

  1. additionnbutanol (10 ml) was added
  2. additionthe whole mix
  3. temperatureheated up
  4. temperatureto reflux
  5. temperaturereflux
  6. temperatureto cool
  7. extractionextracted with dichloromethane (3×100 ml)
  8. dry with materialThe combined organic extracts were dried over Na2SO4
  9. customevaporated in vacuo
  10. customto give a dark oil which
  11. customwas chromatographed on silica gel (˜200 g)
  12. washeluting from 20% ethyl acetate in hexane

Sources & evidence

ORD record
ord-a69b9494b7be4586bf03d941ab34e586
Source dataset
uspto-grants-2005_09
Patent number
US06939871B2

Reaction notes

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