Hydrochloric Acid → 5-Bromo-6-cyclobutoxynicotinic acid

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Reaction Steps

In a 250 mL pear-shaped flask, 5-bromo-6-chloronicotinic acid (5 g, 21.1 mmol, Eq: 1.00) was combined with DMSO (75 mL) to give a colorless solution. Potassium hydroxide (3.56 g, 63.4 mmol, Eq: 3) powdered and cyclobutanol (1.98 g, 2.15 ml, 27.5 mmol, Eq: 1.3) were added and the reaction mixture was stirred at RT overnight (->yellow solution). TLC indicated the reaction to be complete. The mixture was diluted with 75 ml H2O, cooled to 0-5° C., and neutralized with 8 ml 25% HCl (slowly added dropwise under stirring whereupon a white solid formed). The solid was filtered off, washed with 2×20 mL H2O and dried overnight on HV; thereby, 5.26 g of 5-bromo-6-cyclobutoxy-nicotinic acid was obtained as white solid; MS (EI) 272.2, 274.2 (M+H)+.

Provenance & Evidence