5-Methylpyrazin-2-amine → (S)-2-(tert-butyldimethylsilyloxy)-3-ethoxy-N-(5-methylpyrazin-2-yl)propanamide

Beteiligte Stoffe

Reaktionsschritte

A solution of trimethylaluminium (2M in hexane, 5.51 mL, 11.02 mmol) was added dropwise to a stirred solution of 5-methylpyrazin-2-amine (CAS no. 5521-58-4) (1.20 g, 11.0 mmol) in toluene (20 mL) cooled to 0° C., over a period of 5 minutes under nitrogen. The resulting solution was stirred for 15 minutes. A solution of (S)-methyl 2-(tert-butyldimethylsilyloxy)-3-ethoxypropanoate (Intermediate G3) (2.63 g, 10.0 mmol) in toluene (5 mL) was added dropwise over a period of 2 minutes. The resulting solution was allowed to warm to ambient temperature and then heated to reflux for 3 hours. 20% Sodium potassium tartrate solution (50 mL) then water (25 mL) were added and the mixture extracted with ethyl acetate (25 mL). The aqueous was re-extracted with ethyl acetate (25 mL). The organic phases were combined, washed with water (5 mL) and brine (20 mL), dried (MgSO4) and evaporated The residue was purified by flash silica chromatography, elution gradient 20 to 100% EtOAc in isohexane to give (2S)-2-(tert-butyl-dimethylsilyl)oxy-3-ethoxy-N-(5-methylpyrazin-2-yl)propanamide (1.45 g, 42%).

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