Water → N-(5-chloro-4-methyl-pyridin-2-yl)-2,2-dimethyl-propionamide

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Reaction Conditions

Reaction Steps

2,2-Dimethyl-N-(4-methyl-pyridin-2-yl)-propionamide (42 g, 0.22 mol) from Step 1 was placed in a 3-neck 3 L flask fitted with an overhead stirrer. To this was added water (650 mL), then Na2HPO4 (78 g, 0.55 mol), followed by DCM (220 mL). The mixture was stirred and cooled in an ice-bath to 0° C., then chlorine gas was bubbled slowly through a sparge-frit. The reaction was monitored by TLC (EtOAc/hexanes 1/1), and found to be complete after 80 min. The reaction mixture was poured into a separatory funnel and extracted. The aqueous layer was re-extracted with DCM (2×100 mL). The combined layers were dried over Na2SO4 and concentrated to a crude solid product which was recrystallized from hexanes to yield the purified N-(5-chloro-4-methyl-pyridin-2-yl)-2,2-dimethyl-propionamide (41 g, 0.18 mol). 1H NMR (CDCl3) δ 8.18 (s, 1 H), 8.12 (s, 1 H), 7.94 (br s, 1 H), 2.35 (s, 3H), 1.29 (s, 9H).

Provenance & Evidence