Hydrochloric Acid → 2-(4-((6-Fluoro-2-quinolinyl)oxy)phenoxy)-N-(4-(trifluoromethoxy)phenyl)propanamide

HRID 1655539Notes

Reaction equation

HRID 1655539 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([O:12][C:13]1[CH:24]=[CH:23][C:16]([O:17][CH:18]([CH3:22])[C:19](Cl)=[O:20])=[CH:15][CH:14]=1)[CH:6]=[CH:5]2.Cl.[F:26][C:27]([F:37])([F:36])[O:28][C:29]1[CH:35]=[CH:34][C:32]([NH2:33])=[CH:31][CH:30]=1.C(N(CC)CC)C.Cl>C(Cl)Cl>[F:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([O:12][C:13]1[CH:24]=[CH:23][C:16]([O:17][CH:18]([CH3:22])[C:19]([NH:33][C:32]3[CH:34]=[CH:35][C:29]([O:28][C:27]([F:26])([F:36])[F:37])=[CH:30][CH:31]=3)=[O:20])=[CH:15][CH:14]=1)[CH:6]=[CH:5]2

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 27810604-(trifluoromethoxy)aniline HydrochlorideHCID 150701622-(4-((6-Fluoro-2-quinolinyl)oxy)phenoxy)propionyl chloride

Product 1

HCID 197926932-(4-((6-Fluoro-2-quinolinyl)oxy)phenoxy)-N-(4-(trifluoromethoxy)phenyl)propanamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of 5 mmol of 2-(4-((6-fluoro-2-quinolinyl)oxy)phenoxy)propionyl chloride in 5 milliliters (ml) of methylene chloride was slowly added to an ice-cooled solution comprising 1.17 grams (g) (5.5 mmol) of 4-(trifluoromethoxy)aniline hydrochloride and 1.21 g (12 mmol) of triethylamine in 40 ml of methylene chloride. The reaction mixture was stirred at 0° C. for 30 minutes then at room temperature for 3 hours. The mixture was poured into a dilute aqueous HCl solution. The organic layer was separated, washed with water, then washed with a saturated aqueous NaHCO3 solution, dried over MgSO4 and evaporated to dryness. The residual solid was taken up in methylene chloride and filtered through a short column of silica gel, eluting with additional methylene chloride. After removal of the solvent, the residue was recrystallized from methylcyclohexane to give 1.0 g (41 percent of theoretical) of the above-named product as colorless crystals. The product melted at 134°-136° C. and its structure was confirmed by its infrared (IR) and its nuclear magnetic resonance (NMR) spectrum. (Compound 3)

Workup

  1. temperaturecooled solution
  2. waitat room temperature for 3 hours
  3. customThe organic layer was separated
  4. washwashed with water
  5. washwashed with a saturated aqueous NaHCO3 solution
  6. dry with materialdried over MgSO4
  7. customevaporated to dryness
  8. filtrationfiltered through a short column of silica gel
  9. washeluting with additional methylene chloride
  10. customAfter removal of the solvent
  11. customthe residue was recrystallized from methylcyclohexane

Sources & evidence

ORD record
ord-df4242359d1341ea8b2eb59bac89b7af
Source dataset
uspto-grants-1993_10
Patent number
US05250690

Reaction notes

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