Reaktion #608020

Reaktionsgleichung

5-bromo-1-methyl-1H-imidazole

isopropylmagnesium chloride lithium chloride

N-methoxy-N-methyl-6-(trifluoromethyl)nicotinamide

Intermediate 4

N-methoxy-N-methyl-6-(trifluoromethyl)nicotinamide

→

title compound

(1-Methyl-1H-imidazol-5-yl)(6-(trifluoromethyl)pyridin-3-yl)methanone

Lösungsmittel

THF

THF

THF

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeTo a 3 L 4-neck flask equipped with an overhead stirrer
2. 2
   Sonstigeto afford a milky suspension
3. 3
   Sonstigeto afford an orange mixture
4. 4
   workup.ADDITIONAfter addition
5. 5
   Temperaturthe reaction was warmed to room temperature over 2 hours
6. 6
   workup.STIRRINGAfter stirring at room temperature for 18 hours
7. 7
   workup.STIRRINGthe reaction was stirred for 2 hours
8. 8
   TemperaturThe reaction was then cooled to 4° C. with an ice bath
9. 9
   Sonstigecarefully quenched with 2 N aqueous HCl to pH=7
10. 10
    Sonstigequenching temperature
11. 11
    Sonstigereached 12° C
12. 12
    workup.ADDITIONThe mixture was diluted with ethyl acetate (500 mL)
13. 13
    Sonstigethe phases were separated
14. 14
    Waschenthe organic layer was washed with brine (2×200 mL)
15. 15
    Trocknendried over sodium sulfate
16. 16
    Filtrationfiltered
17. 17
    Sonstigethe solvent was removed
18. 18
    workup.ADDITIONHot ether was added
19. 19
    Filtrationfiltered

Vorschrift

To a 3 L 4-neck flask equipped with an overhead stirrer, nitrogen bubbler, and thermocouple was added 5-bromo-1-methyl-1H-imidazole (47.96 g, 297.9 mmol), followed by THF (537 mL). To this room temperature solution was added isopropylmagnesium chloride/lithium chloride complex (246.8 mL, 320.8 mmol, 1.3 M in THF) (addition temperature maintained between 16.6 and 25° C.) to afford a milky suspension and the reaction was stirred for 60 minutes and then cooled to 5.3° C. in an ice bath. To this mixture was added a solution of N-methoxy-N-methyl-6-(trifluoromethyl)nicotinamide (53.66 g, 229.1 mmol, Intermediate 4: step b) in THF (268 mL) (addition temperature between 5.3 and 5.6° C.) to afford an orange mixture. After addition, the reaction was warmed to room temperature over 2 hours. After stirring at room temperature for 18 hours, THF (200 mL) was added and the reaction was stirred for 2 hours. The reaction was then cooled to 4° C. with an ice bath and carefully quenched with 2 N aqueous HCl to pH=7, quenching temperature reached 12° C. The mixture was diluted with ethyl acetate (500 mL), the phases were separated, and the organic layer was washed with brine (2×200 mL) and dried over sodium sulfate, filtered and the solvent was removed. Hot ether was added and then filtered to give the title compound as a solid.

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