Potassium bis(trimethylsilyl)amide → 5-Methyl-3-phenylimidazo[1,2-a]pyridin-2-ol

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Reaction Steps

2-Chloro-N-(6-methylpyridin-2-yl)-2-phenylacetamide (11.5 g, ˜80%, see step 1) was dissolved in 167 mL anhydrous THF. After addition of tetra-n-butyl ammonium iodide (700 mg, 1.90 mmol) the reaction mixture was cooled with ice-water. 2.5 Equivalents potassium bis(trimethylsilyl)amide as a 0.5M solution in THF (95 mL, 47.4 mmol) were added dropwise. The reaction mixture was stirred for 10 min at room temperature and for additional 2h at reflux. The reaction mixture was cooled to room temperature and partitioned between ethyl acetate and an 1M aqueous solution of citric acid. The organic phase was washed with brine and dried with sodium sulphate. LC-MS analysis showed that the predominant portion of the title compound was still remaining in the aqueous phase. The aqueous phase was therefore neutralized with 1M sodium hydroxide solution. After extraction with dichloromethane (2×) the combined organic phases were washed with brine and dried with sodium sulphate. The residue was triturated with hot ethyl acetate and was filtered while being hot. The filtrate was concentrated in vacuo. After drying under high vacuum 2.70 g (26%) of the title compound were observed.

Provenance & Evidence