Hydrochloric Acid → HCID 178522156, compound

HRID 2384323Notes

Reaction equation

HRID 2384323 reaction equation
[Cl:1][C:2]1[CH:3]=[N:4][C:5]([OH:11])=[C:6]([CH:10]=1)[C:7]([OH:9])=O.[F:12][C:13]([F:26])([F:25])[C:14]1[CH:15]=[C:16]([CH:18]=[C:19]([C:21]([F:24])([F:23])[F:22])[CH:20]=1)[NH2:17].N1C=CC=CC=1.P(Cl)(Cl)(Cl)=O.Cl>O1CCCC1.ClCCl.C(OCC)(=O)C>[F:12][C:13]([F:25])([F:26])[C:14]1[CH:15]=[C:16]([NH:17][C:7]([C:6]2[C:5]([OH:11])=[N:4][CH:3]=[C:2]([Cl:1])[CH:10]=2)=[O:9])[CH:18]=[C:19]([C:21]([F:22])([F:24])[F:23])[CH:20]=1

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 1049PyridineHCID 9480Benzenamine, 3,5-bis(trifluoromethyl)-HCID 24813Phosphorus oxychlorideHCID 178524411HCID 178524411, compound

Product 1

HCID 178522156HCID 178522156, compoundYield 47.6%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

5-Chloro-2-hydroxynicotinic acid (174 mg, 1 mmol), 3,5-bis(trifluoromethyl)aniline (275 mg, 1.2 mmol) and pyridine (316 mg, 4 mmol) were dissolved in tetrahydrofuran (20 mL) and dichloromethane (10 mL). Phosphorus oxychloride (0.112 ml, 1.2 mmol) was added, and the mixture was stirred at room temperature for 2 hours. The reaction mixture was poured into ethyl acetate (100 mL) and 0.2 N hydrochloric acid (100 mL), filtered through celite after stirring for 30 minutes, and the water layer of the filtrate was extracted with ethyl acetate. After the combined ethyl acetate layer was washed with water and brine one after another, dried over anhydrous magnesium sulfate, the solvent was evaporated under reduced pressure. The residue was purified by column chromatography on silica gel (n-hexane:ethyl acetate=2:1→1:1) to give a light yellow solid. This was suspended and washed with ethanol under heating at reflux to give the title compound (183 mg, 47.6%) as a white crystal.

Workup

  1. filtrationfiltered through celite
  2. stirringafter stirring for 30 minutes
  3. extractionthe water layer of the filtrate was extracted with ethyl acetate
  4. washAfter the combined ethyl acetate layer was washed with water and brine one after another,
  5. dry with materialdried over anhydrous magnesium sulfate
  6. customthe solvent was evaporated under reduced pressure
  7. customThe residue was purified by column chromatography on silica gel (n-hexane:ethyl acetate=2:1→1:1)
  8. customto give a light yellow solid
  9. washwashed with ethanol
  10. temperatureunder heating
  11. temperatureat reflux

Sources & evidence

ORD record
ord-2fbfbd34171e459cb798e88e122d8456
Source dataset
uspto-grants-2012_09
Patent number
US08263657B2

Reaction notes

Loading…