Reaktion #2468667

Reaktionsgleichung

N-methylaniline

4,5-dichloro-2-(tetrahydropyran-2-yl)-2H-pyridazin-3-one

Intermediate 20

4,5-dichloro-2-(tetrahydropyran-2-yl)-2H-pyridazin-3-one

sodium tert-butoxide

→

4-chloro-5-(methyl-phenyl-amino)-2-(tetrahydro-pyran-2-yl)-2H-pyridazin-3-one

Ausbeute 11.0%

Lösungsmittel

toluene

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigein a glass reaction tube
2. 2
   Sonstigewas fitted with a septa
3. 3
   Sonstigeevacuated via house vacuum
4. 4
   Sonstigeflush three times
5. 5
   Sonstigeto remove air from the reaction system
6. 6
   TemperaturAfter this time, the reaction was cooled to 25° C. where it
7. 7
   SonstigeAfter this time, the reaction mixture was then partitioned between water (200 mL) and ethyl acetate (200 mL)
8. 8
   ExtraktionThe aqueous layer was back extracted with ethyl acetate (100 mL)
9. 9
   TrocknenThe combined organics were dried over magnesium sulfate
10. 10
    Filtrationfiltered
11. 11
    Einengenconcentrated in vacuo

Vorschrift

A mixture of 4,5-dichloro-2-(tetrahydropyran-2-yl)-2H-pyridazin-3-one (2.0 g, 8.02 mmol) (Intermediate 20), sodium tert-butoxide (0.93 g, 9.67 mmol), tris(dibenzylideneacetone)dipalladium(0) (19 mg, 0.02 mmol) and N-phenyl-2-(di-tert-butylphosphino)indole (27.4 mg, 0.08 mmol) in a glass reaction tube was fitted with a septa and then evacuated via house vacuum followed by a nitrogen flush three times to remove air from the reaction system. The reaction was then treated with anhydrous toluene (8 mL, 1.0M) and N-methylaniline (1.05 mL, 9.69 mmol). The reaction was heated to 120° C. for 4 d. After this time, the reaction was cooled to 25° C. where it stirred for an additional 1 d. After this time, the reaction mixture was then partitioned between water (200 mL) and ethyl acetate (200 mL). The aqueous layer was back extracted with ethyl acetate (100 mL). The combined organics were dried over magnesium sulfate, filtered, and concentrated in vacuo. Silica gel column chromatography (AnaLogix, 115 g, 10-40% ethyl acetate/hexanes gradient) afforded 4-chloro-5-(methyl-phenyl-amino)-2-(tetrahydro-pyran-2-yl)-2H-pyridazin-3-one (277.2 mg, 11%) as an orange/red oil.

Quelle