3,4-dihydro-2H-pyran → 3-bromo-2-methyl-6-(1-(tetrahydro-2H-pyran-2-yl)-1H-1,2,4-triazol-3-yl)pyridine

HRID 1047266Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1047266
[Br:1][C:2]1[C:3]([CH3:13])=[N:4][C:5]([C:8]2[N:12]=[CH:11][NH:10][N:9]=2)=[CH:6][CH:7]=1.[O:14]1[CH:19]=[CH:18][CH2:17][CH2:16][CH2:15]1>O1CCCC1.C(OCC)(=O)C.CCCCCC.C(O)(C(F)(F)F)=O>[Br:1][C:2]1[C:3]([CH3:13])=[N:4][C:5]([C:8]2[N:12]=[CH:11][N:10]([CH:15]3[CH2:16][CH2:17][CH2:18][CH2:19][O:14]3)[N:9]=2)=[CH:6][CH:7]=1

Komponenten

7

Edukt 2

HCID 80803,4-dihydro-2H-pyranHCID 178432644HCID 178432644, Verbindung

Produkt 1

HCID 582983093-bromo-2-methyl-6-(1-(tetrahydro-2H-pyran-2-yl)-1H-1,2,4-triazol-3-yl)pyridineAusbeute 42 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 6422Trifluoroacetic acidKatalysatorHCID 8028TetrahydrofuranLösungsmittelHCID 8058HexaneLösungsmittelHCID 8857Ethyl AcetateLösungsmittel2×

Reaktionsbedingungen

Temperatur
70 °C

Versuchsvorschrift

3-Bromo-2-methyl-6-(1H-1,2,4-triazol-3-yl)pyridine (0.7 g, 2.93 mmol) and 3,4-dihydro-2H-pyran (0.493 g, 5.86 mmol) were dissolved in tetrahydrofuran (20 mL). TFA (3.34 mg, 0.029 mmol) was added and the resulting solution was heated to 70° C. for 16 h. The reaction mixture was cooled to room temperature, diluted with ethyl acetate, filtered and poured into a separatory funnel containing water and ethyl acetate. The organic layer was concentrated under reduced pressure. Flash chromatography (0-60% ethyl acetate in hexane) gave the desired product as a white solid (0.40 g, 1.23 mmol, 42% yield). MS (ESI) m/z 325.1 [M+2]+. Alternate approach: 3-Bromo-2-methyl-6-(1H-1,2,4-triazol-3-yl)pyridine (1 equiv), 3,4-dihydro-2H-pyran (2 equiv) and methanesulfonic acid (0.08 equiv) were combined in tetrahydrofuran (8×vol). The solution was heated and stirred at 68° C. for 3.5 h then cooled to room temperature. Triethylamine (0.4 equiv) was added and the resulting solution was concentrated under reduced pressure to an oil. The oil was treated with acetonitrile and concentrated under reduced pressure iteratively until a solid was obtained. The solid was dissolved in acetonitrile and treated with water. The suspension was filtered and the solids were collected and dried. The crude product was slurried in hexanes, filtered and dried to give the purified title compound as a light pink solid.

Aufarbeitung

  1. temperatureThe reaction mixture was cooled to room temperature
  2. filtrationfiltered
  3. additionpoured into a separatory funnel
  4. additioncontaining water and ethyl acetate
  5. concentrationThe organic layer was concentrated under reduced pressure

Quellen und Nachweise

ORD-Eintrag
ord-de82fdcda4b145389eca83e75e89de76
Quelldatensatz
uspto-grants-2013_10
Patentnummer
US08569494B2

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