Réaction #2044989

Équation de réaction

methyl-p-toluenesulfonate

4-methoxy-2-(1H-imidazol-2-yl)pyridine

NaH

→

4-methoxy-2-(1-methyl-1H-imidazol-2-yl)pyridine

Rendement 46.4%

Solvants

DMF

DMF

Conditions de réaction

Traitement

1. 1
   workup.STIRRINGwith stirring
2. 2
   workup.WAITAfter 15 min
3. 3
   Autrethe ice bath was removed
4. 4
   workup.STIRRINGthe reaction mixture stirred for 2 h at room temp
5. 5
   TempératureCooled back to 0° C.
6. 6
   Autrequenched
7. 7
   workup.ADDITIONby very carefully adding 10% aq. Na2CO3 dropwise (about 10 mL total)
8. 8
   ExtractionExtracted 2×30 mL chloroform
9. 9
   LavageCombined organic layers were washed with brine (5 mL)
10. 10
    Séchagedried over Na2SO4
11. 11
    Concentrationconcentrated
12. 12
    Autreto give 0.73 g as a dual-phase oil
13. 13
    AutreChromatographed on 18 g silica gel in 0-2% MeOH/CHCl3+0.5% TEA

Mode opératoire

To crude 4-methoxy-2-(1H-imidazol-2-yl)pyridine (0.40 g, 2.28 mmol) in 7.5 mL anhydrous DMF with magnetic stirring under Ar at 0° C., NaH (60% in oil, 91 mg, 2.28 mmol) was added portionwise. Stirred at 0-5° C. for 1 h, then added a solution of methyl-p-toluenesulfonate (0.344 mL, 2.28 mmol) in 0.75 mL anh. DMF dropwise with stirring. After 15 min, the ice bath was removed and the reaction mixture stirred for 2 h at room temp. Cooled back to 0° C. and quenched by very carefully adding 10% aq. Na2CO3 dropwise (about 10 mL total). Extracted 2×30 mL chloroform. Combined organic layers were washed with brine (5 mL), dried over Na2SO4 and concentrated to give 0.73 g as a dual-phase oil. Chromatographed on 18 g silica gel in 0-2% MeOH/CHCl3+0.5% TEA to yield 0.20 g (45%) of 4-methoxy-2-(1-methyl-1H-imidazol-2-yl)pyridine.

Source