Acetic Anhydride → 2-Methyl-6-(1H-1,2,4-triazol-1-yl)pyridin-3-yl acetate

HRID 1931574

Reaktionsgleichung

Reaktionsgleichung von HRID 1931574
B(F)(F)F.CCOCC.[CH3:10][C:11]1[C:16](N)=[CH:15][CH:14]=[C:13]([N:18]2[CH:22]=[N:21][CH:20]=[N:19]2)[N:12]=1.N(OC(C)(C)C)=O.[C:30]([O:33]C(=O)C)(=[O:32])[CH3:31]>CN(C)C=O.COCCOC.CCCCCC>[CH3:10][C:11]1[C:16]([O:33][C:30](=[O:32])[CH3:31])=[CH:15][CH:14]=[C:13]([N:18]2[CH:22]=[N:21][CH:20]=[N:19]2)[N:12]=1

Komponenten

8

Edukt 4

HCID 7918Acetic AnhydrideHCID 8000Boron trifluoride etherateHCID 10906Tert-Butyl nitriteHCID 532992722-methyl-6-(1H-1,2,4-triazol-1-yl)pyridin-3-amine

Produkt 1

HCID 669152932-Methyl-6-(1H-1,2,4-triazol-1-yl)pyridin-3-yl acetateAusbeute 50,2 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 6228DimethylformamideLösungsmittelHCID 8058HexaneLösungsmittelHCID 80711,2-DimethoxyethaneLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

A solution of boron trifluoride etherate (217 μL, 1.7 mmol) in dimethylformamide (1 mL) was cooled to −15° C. using an ice-acetonitrile bath, and then stirred for 15 min at this temperature. A solution of 2-methyl-6-[1,2,4]triazol-1-yl-pyridin-3-ylamine (from Step 2; 200 mg, 1.14 mmol) in 1,2-dimethoxyethane (7 mL) was added dropwise to the solution at −15° C. and the stirring was continued for a further 15 min. tert-Butyl nitrite (Aldrich Chemical Company, Inc., Milwaukee, Wis., USA 90%; 157 mg, 1.4 mmol) was added dropwise, and the reaction mixture was stirred at −15° C. for 15 min and then at 0° C. for 1 h. Hexane (10 mL) was added and the solid was filtered off, washed with hexane, and air-dried. The solid was added to acetic anhydride (5 g, 49 mmol) and the mixture was heated at 100° C. for 1.5 h. The acetic anhydride was evaporated under high vacuum and then 1 M aqueous sodium carbonate solution was added. The mixture was extracted three times with dichloromethane. The dichloromethane was evaporated and the residue was purified by silica gel column chromatography, eluting with 0-40% ethyl acetate/hexane to give acetic acid 2-methyl-6-[1,2,4]triazol-1-yl-pyridin-3-yl ester (125 mg, 50%). 1H NMR (CDCl3) δ 2.38 (s, 3H), 2.46 (s, 3H), 7.56 (d, 1H, J=8.8 Hz), 7.77 (d, 1H, J=8.6 Hz), 8.10 (s, 1H), 9.16 (s, 1H).

Aufarbeitung

  1. waitthe stirring was continued for a further 15 min.
  2. stirringthe reaction mixture was stirred at −15° C. for 15 min
  3. waitat 0° C. for 1 h
  4. filtrationthe solid was filtered off
  5. washwashed with hexane
  6. customair-dried
  7. customThe acetic anhydride was evaporated under high vacuum
  8. addition1 M aqueous sodium carbonate solution was added
  9. extractionThe mixture was extracted three times with dichloromethane
  10. customThe dichloromethane was evaporated
  11. customthe residue was purified by silica gel column chromatography
  12. washeluting with 0-40% ethyl acetate/hexane

Quellen und Nachweise

ORD-Eintrag
ord-337ac2af9d3b46d5b25e91a7f4c65eb6
Quelldatensatz
uspto-grants-2012_05
Patentnummer
US08188098B2

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