Diethyl Malonate → Diethyl 2-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)malonate

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Reaction Steps

To a suspension of 60% sodium hydride in mineral oil (5.28 g) in dry dimethylformamide (50 ml) at 0° C. was added a solution of diethyl malonate (10 ml) in dry dimethylformamide (25 ml) and the mixture was stirred for 30 minutes. A solution of 2,3-dichloro-5-(trifluoromethyl)pyridine (9.8 ml) in dry dimethylformamide (10 ml) was added dropwise and the mixture warmed with stirring to 22° C. over 18 hours. Acetic acid (7.5 ml) in diethyl ether (20 ml) was added dropwise and the mixture was stirred until hydrogen evolution had ceased. The mixture was diluted with diethyl ether (600 ml) and then water washed (3×200 ml). The organic extract was dried (MgSO4) and evaporated onto flash silica. Chromatography over silica eluting with 0-20% diethyl ether in light petroleum (b.p. 40-60° C.) gave the title compound. 1H N.M.R. (CDCl3) δ(ppm) 1.28 (6H, t, 2×CH3CH2), 4.30 (4H, q, 2×CH2CH3), 5.24 (1H, s, CH(CO2Et)2), 7.96 (1H, s, py-H), 8.74 (1H, s, py-H).

Provenance & Evidence