Oxalyl chloride → 5-[1-(4-methoxyphenyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl]2-methylpyridine

HRID 584726

Reaktionsgleichung

Reaktionsgleichung von HRID 584726
[CH3:1][C:2]1[CH:10]=[CH:9][C:5]([C:6](O)=O)=[CH:4][N:3]=1.C(Cl)(=O)C(Cl)=O.[F:17][C:18]([F:32])([F:31])[C:19](=[N:21][NH:22][C:23]1[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[CH:25][CH:24]=1)[NH2:20].C(N(C(C)C)CC)(C)C>ClCCl.O1CCOCC1.CN(C)C=O>[CH3:30][O:29][C:26]1[CH:25]=[CH:24][C:23]([N:22]2[C:6]([C:5]3[CH:9]=[CH:10][C:2]([CH3:1])=[N:3][CH:4]=3)=[N:20][C:19]([C:18]([F:17])([F:31])[F:32])=[N:21]2)=[CH:28][CH:27]=1

Komponenten

8

Edukt 4

HCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 1378606-Methylnicotinic acidHCID 696776222,2,2-trifluoro-N'-(4-methoxyphenyl)ethanehydrazonamide

Produkt 1

HCID 223415735-[1-(4-methoxyphenyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl]2-methylpyridineAusbeute 15,3 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 6228DimethylformamideLösungsmittelHCID 6344DichloromethaneLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Versuchsvorschrift

To a suspension of 6-methylnicotinoic acid (329 mg, 2.4 mmol) in dichloromethane (3 mL), was added oxalyl chloride (0.209 mL, 2.4 mmol). And then 10 micro-L of dimethylformamide was added to the mixture. The mixture was stirred for 1 hour and the solvent was removed under reduced pressure. The residue was azeotroped with dichloromethane. To the residue, was added 3 mL of dioxane. Then a solution of 2,2,2-trifluoro-N′-(4-methoxyphenyl)ethanehydrazonamide (466 mg, 2 mmol) and diisopropylethylamine (0.418 mL, 2.4 mmol) in 4.5 mL of dioxane was added to the mixture and the mixture was refluxed with stirring for 3.5 hours. The solvent was removed under reduced pressure, and dichloromethane and 0.1 N hydrochloric acid were added to the residue. The organic layer was separated, washed with 0.1 N hydrochloric acid, water, and brine, dried over magnesium sulfate. The crude product was purified by silica gel column chromatography (8:1 toluene-ethyl acetate). The desired product was rinsed with hexane and dried in vacuo to give 5-[1-(4-methoxyphenyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl]2-methylpyridine (102 mg, 14.8% yield).

Aufarbeitung

  1. customthe solvent was removed under reduced pressure
  2. customThe residue was azeotroped with dichloromethane
  3. additionTo the residue, was added 3 mL of dioxane
  4. temperaturethe mixture was refluxed
  5. stirringwith stirring for 3.5 hours
  6. customThe solvent was removed under reduced pressure, and dichloromethane and 0.1 N hydrochloric acid
  7. additionwere added to the residue
  8. customThe organic layer was separated
  9. washwashed with 0.1 N hydrochloric acid, water, and brine
  10. dry with materialdried over magnesium sulfate
  11. customThe crude product was purified by silica gel column chromatography (8:1 toluene-ethyl acetate)
  12. washThe desired product was rinsed with hexane
  13. customdried in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-ea8c156a96844c9a98f31272410485c5
Quelldatensatz
uspto-grants-2005_08
Patentnummer
US06927230B2

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