Potassium Hydroxide → 4-(4-Chloro-2-fluorophenoxy)-6-methoxy-7-(2-([1,2,4]-triazol-1-yl)ethoxy)quinoline hydrochloride

HRID 393641

Reaction equation

HRID 393641 reaction equation
[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:14][CH2:15][CH2:16][N:17]3[CH:21]=[N:20][CH:19]=[N:18]3)=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[CH:4][CH:3]=1.[Cl:22][C:23]1[CH:28]=[CH:27][C:26]([OH:29])=[C:25]([F:30])[CH:24]=1.[OH-].[K+]>>[ClH:1].[Cl:22][C:23]1[CH:28]=[CH:27][C:26]([O:29][C:2]2[C:11]3[C:6](=[CH:7][C:8]([O:14][CH2:15][CH2:16][N:17]4[CH:21]=[N:20][CH:19]=[N:18]4)=[C:9]([O:12][CH3:13])[CH:10]=3)[N:5]=[CH:4][CH:3]=2)=[C:25]([F:30])[CH:24]=1

Participants

4

Reactant 3

HCID 14797Potassium HydroxideHCID 1819754-Chloro-2-fluorophenolHCID 226465544-Chloro-6-methoxy-7-(2-([1,2,4]-triazol-1-yl)ethoxy)quinoline

Product 1

HCID 226466014-(4-Chloro-2-fluorophenoxy)-6-methoxy-7-(2-([1,2,4]-triazol-1-yl)ethoxy)quinoline hydrochlorideYield 61%

Procedure

A mixture of 4-chloro-6-methoxy-7-(2-([1,2,4]-triazol-1-yl)ethoxy)quinoline (132 mg, 0.43 mmol), 4-chloro-2-fluorophenol (400 mg, 2.7 mmol) and potassium hydroxide (28 mg, 0.49 mmol) was head at 165° C. for 3 hours under argon. The mixture was partitioned between ethyl acetate and water. The organic layer was washed with water, brine, dried (MgSO4) and the volatiles were removed by evaporation. The residue was purified by column chromatography eluting with methylene chloride/methanol (95/5). The purified product was dissolved in methylene chloride and 2M ethereal hydrogen chloride (0.5 ml) was added. The volatiles were removed by evaporation and the residue was triturated with ether, collected by filtration and dried under vacuum to give 4-(4-chloro-2-fluorophenoxy)-6-methoxy-7-(2-([1,2,4]-triazol-1-yl)ethoxy)quinoline hydrochloride (110 mg, 61%).

Workup

  1. customat 165° C.
  2. customfor 3 hours
  3. customThe mixture was partitioned between ethyl acetate and water
  4. washThe organic layer was washed with water, brine
  5. dry with materialdried (MgSO4)
  6. customthe volatiles were removed by evaporation
  7. customThe residue was purified by column chromatography
  8. washeluting with methylene chloride/methanol (95/5)
  9. dissolutionThe purified product was dissolved in methylene chloride
  10. addition2M ethereal hydrogen chloride (0.5 ml) was added
  11. customThe volatiles were removed by evaporation
  12. customthe residue was triturated with ether
  13. filtrationcollected by filtration
  14. customdried under vacuum

Sources & evidence

ORD record
ord-e9ad687a37674a76836f2bf397f7b46e
Source dataset
uspto-grants-2004_10
Patent number
US06809097B1

Linked notes

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