Hydrochloric Acid → N-[5-(2-Chloroacetyl)-2-pyridinyl]acetamide

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Reaction Steps

Sodium chloroacetate (5.2 g, 0.045 mol) and 4.3 g (0.045 mol) of magnesium chloride were added to a solution of 5.8 g (0.030 mol) of methyl 6-(methylcarboxamido)pyridine-3-carboxylate in 100 ml of THF, and the mixture was stirred at room temperature for 3 hours. Magnesium diisopropylamide chloride solution [solution prepared by adding 20 ml (0.144mol) of diisopropylamine drop wise at 40° C. to 67 ml (0.120 mol) of a 1.8 M/kg n-butylmagnesium chloride solution in THF, followed by 3 hours of stirring at 40° C. ] was added drop wise to this solution at 0° C. over 30 minutes, and the mixture was stirred at room temperature for 27 hours. A solution prepared by dissolving 25 ml (0.300 mol) of concentrated hydrochloric acid in 50 ml of water was added drop wise to the reaction mixture at 0° C. The resulting mixture was extracted with ethylacetate, and the or ganicphase was washed with a saturated aqueous solution of sodium hydrogen carbonate aqueous solution and dried over sodium sulfate. The solvent was distilled off under reduced pressure and the product was isolated and purified by silica gel column chromatography (hexane:ethyl acetate=1:1) to give 4.5 g (yield 71%) of the desired N1-[5-(2-chloroacetyl)pyridin-2-yl]ethanamide. 1H-NMR (400 MHz, DMSO-d6) δ 10.93 (1H, s), 8.90 (1H, s), 8.29 (1H, d, J=8.8 Hz), 8.19 (1H, d, J=8.8 Hz), 5.16 (2H, s), 2.13 (3H, s). 13C-NMR (100 MHz, DMSO-d6) δ 189.7, 170.1, 155.4, 149.4, 138.4, 125.6, 112.5, 47.4, 24.1. IR (KBr) 1690 cm−1.

Provenance & Evidence