Reaction #87402

Reaction equation

5-(4-Bromo-2-methoxyphenyl)-3-methylpyridazine

sodium tert-butoxide

benzophenone imine

Sodium carbonate

NaOAc

ammonium

→

title compound

Yield 93.0%

3-Methoxy-4-(6-methylpyridazin-4-yl)aniline

Yield 93.0%

Solvents

toluene

Conditions

Workup

1. 1
   OtherThe flask was purged with N2 three times
2. 2
   Temperaturecooled down
3. 3
   Filtrationfiltered through a pad of diatomaceous earth
4. 4
   Washthe filter was washed with MTBE
5. 5
   ConcentrationThe filtrate was concentrated
6. 6
   workup.DISSOLUTIONThe residue was dissolved in MeOH (60 mL)
7. 7
   workup.STIRRINGThe mixture was stirred at room temperature for 1 hour
8. 8
   workup.STIRRINGthe mixture was stirred at room temperature for 10 minutes
9. 9
   Concentrationconcentrated under reduced pressure
10. 10
    WashThe organic phase was washed with water, brine
11. 11
    Dryingdried over sodium sulfate
12. 12
    Otherthe solvent was removed under reduced pressure
13. 13
    OtherThe residue was purified by flash chromatography on silica gel
14. 14
    Washeluting with 0% to 1% methanol in ethyl acetate

Procedure

5-(4-Bromo-2-methoxyphenyl)-3-methylpyridazine (1.72 g, 6.20 mmol), Pd2(dba)3 (57 mg, 0.062 mmol), BINAP (116 mg, 0.19 mmol), sodium tert-butoxide (833 mg, 8.68 mmol), benzophenone imine (1.25 mL, 7.44 mmol) and toluene (30 mL) were added into a sealed tube. The flask was purged with N2 three times. The reaction was stirred at 80° C. overnight and then cooled down, filtered through a pad of diatomaceous earth and the filter was washed with MTBE. The filtrate was concentrated. The residue was dissolved in MeOH (60 mL). NaOAc (1.22 g, 14.90 mmol) and ammonium hyxroxide hydrochloride (776 mg, 11.2 mmol) was added. The mixture was stirred at room temperature for 1 hour. Sodium carbonate (1.23 g, 11.60 mmol) was added, and the mixture was stirred at room temperature for 10 minutes and then concentrated under reduced pressure. The residue was taken up in dichloromethane. The organic phase was washed with water, brine, dried over sodium sulfate and the solvent was removed under reduced pressure. The residue was purified by flash chromatography on silica gel, eluting with 0% to 1% methanol in ethyl acetate to afford the title compound 1.24 g (93%) as a solid.

Source