Reacción #44620

Ecuación de reacción

Triphenylphosphonium bromide

acetonitrile

(S)-4-[(S)-1-(2,6-difluoropyridin-3-yl)ethyl]-2-hydroxy-6-methylmorpholin-3-one

3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzaldehyde

→

title compound

Rendimiento 56.6%

(Z)-(S)-4-[(S)-1-(2,6-difluoropyridin-3-yl)ethyl]-2-{1-[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl]methylidene}-6-methylmorpholin-3-one

Rendimiento 56.6%

Disolventes

triethylamine

Condiciones de reacción

Tratamiento posterior

1. 1
   OtroThe resulting reaction solution
2. 2
   Temperaturawas heated
3. 3
   Temperaturaunder reflux for 1 hr
4. 4
   OtroThe resulting reaction solution
5. 5
   Temperaturawas heated
6. 6
   Temperaturaunder reflux for 1.5 hr
7. 7
   Concentraciónconcentrated under reduced pressure
8. 8
   workup.ADDITIONThe residue was diluted with a 2 N hydrochloric acid aqueous solution and ethyl acetate
9. 9
   OtroThe water layer was separated
10. 10
    Lavadothe organic layer was washed with a 2 N hydrochloric acid aqueous solution
11. 11
    ExtracciónThe alkaline aqueous solution was extracted with ethyl acetate
12. 12
    OtroThe organic layer was separated
13. 13
    Lavadowashed with saturated sodium hydrogencarbonate
14. 14
    Secadodried over anhydrous magnesium sulfate
15. 15
    Concentraciónconcentrated under reduced pressure
16. 16
    OtroThe residue was purified by silica gel column chromatography (carrier: Chromatorex NH, eluting solvent; heptane:ethyl acetate=1:1 to 0:1)

Procedimiento

Triphenylphosphonium bromide (6.52 g) was added to an acetonitrile solution of (S)-4-[(S)-1-(2,6-difluoropyridin-3-yl)ethyl]-2-hydroxy-6-methylmorpholin-3-one (4.3 g). The resulting reaction solution was heated under reflux for 1 hr, and triethylamine (5.28 mL) and 3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzaldehyde (3.42 g) were added thereto. The resulting reaction solution was heated under reflux for 1.5 hr and concentrated under reduced pressure. The residue was diluted with a 2 N hydrochloric acid aqueous solution and ethyl acetate. The water layer was separated, and the organic layer was washed with a 2 N hydrochloric acid aqueous solution. All the water layers were combined and alkalinized with a concentrated sodium hydroxide aqueous solution. The alkaline aqueous solution was extracted with ethyl acetate. The organic layer was separated, washed with saturated sodium hydrogencarbonate, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (carrier: Chromatorex NH, eluting solvent; heptane:ethyl acetate=1:1 to 0:1) to give 4.06 g of the title compound. The physical property values of this compound were as follows:

Fuente