Methyl methoxyacetate → 1-[5-Chloro-4-(tetrahydro-pyran-2-yloxymethyl)-pyridin-3-yl]-2-methoxy-ethanone

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Reaction Conditions

Reaction Steps

3-Bromo-5-chloro-4-(tetrahydro-pyran-2-yloxymethyl)-pyridine (0.30 g, 0.98 mmol) was dissolved in anhydrous THF (15 mL) under Ar and the solution was cooled to −78° C. n-BuLi (0.62 mL, 1.6 M in hexanes, 0.98 mmol) was added dropwise and the reaction mixture was stirred at −78° C. for 0.5 h. Then methoxy-acetic acid methyl ester (0.97 mL, 9.8 mmol) dissolved in anhydrous THF (10 mL) was added dropwise and stirring was continued at −78° C. for 2 h. At completion of the reaction, monitored by TLC, saturated NaHCO3 was added with vigorous stirring. The quenched mixture was extracted with EA (2×20 mL) and the combined organic extracts were washed with saturated NaHCO3 (20 mL) and dried over Na2SO4. The residue was purified by flash chromatography on silica gel with EA/hexane to provide the title compound as a colorless oil. MS (m/z): 300.5 [M+H+].

Provenance & Evidence