98552-51-3

98548-81-3

In a round-bottomed flask, ethyl 4-(dimethylamino)but-2-enoate (Formula IV, 120 g) and anhydrous ethanol (480 mL) were added at 25 °C to 35 °C. To this solution, an aqueous sodium hydroxide solution (30.5 g NaOH dissolved in 60 mL of water) was slowly added at 10°C to 20°C. The temperature of the reaction mixture was raised to 50°C and stirred at 50°C to 55°C for 1 hour. Upon completion of the reaction, the mixture was cooled to 5°C and the pH was adjusted slowly to 1.5 by the addition of concentrated hydrochloric acid (120 mL).The reaction mixture was filtered through Celite and the filter cake was washed with ethanol (50 mL). The filtrate was concentrated under reduced pressure at 55°C to 60°C to give the crude product. Ethanol (240 mL) was added to the crude product and stirred at 55°C to 60°C for 15 minutes until complete dissolution, during which time the resulting sodium chloride by-product was removed by filtration. The filtrate was again concentrated under reduced pressure at 55°C to 60°C to give a residue. Isopropanol (400 mL) was added to the residue and stirred at 55°C to 60°C until completely dissolved to form a clarified solution. The solution was slowly cooled to 25°C to 30°C and stirring was continued at this temperature for 2 hours to promote crystallization. The solid product was collected by filtration and washed with cold isopropanol (50 mL). Finally, the solid was dried under vacuum at 55°C to 60°C to give 4-dimethylaminocrotonic acid hydrochloride in 63% yield.