Dimethylamine → (E)-4-dimethylamino Crotonate Hydrochloride

Participants

Reaction Conditions

Reaction Steps

(E)-ethyl 4-bromobut-2-enoate (160 g, 0.83 mol) and methylene chloride (1.6 L) were introduced into 5 L three-neck flask and stirred for 10 minutes at −10° C. 50% Me2NH (187.1 g, 2.5 eq) was extracted by methylene chloride (1.6 L), and water layer was drained. And then, a solution that Me2NH was dissolved in methylene chloride was slowly added as droplets into the flask for 1 hour. At this time, the internal temperature of the reactor was maintained to be 5° C. or less. After all of Me2NH solution dissolved in methylene chloride was added, the degree of the reaction was confirmed with TLC, and the mixture was stirred until the starting materials were not seen. At this time, the stirring required about 30 minutes and it was needed to pay attention that the reaction time did not get long. Water (1280 mL) was added to the reaction solution. The reaction mixture was separated by using a separating funnel, and then the organic layer was washed with an aqueous base solution in which NaOH (66.4 g, 2 eq) dissolved in water (830 mL) and brine solution (800 mL) were mixed. The separated organic layer was dried with anhydrous MgSO4, and then filtered and concentrated. After transferring the concentrated solution into 2 L two-neck flask and dissolving the same in EtOAc (1380 mL), EtOAc solution (222 mL, 1.2 eq) in which 4.5 M HCl was dissolved was slowly added as droplets therein. After the temperature of the reacting flask fell down to room temperature, the reaction mixture was filtered with a filter and the solid left in the filter was washed with EtOAc (500 mL). The solid was transferred into one-neck flask and dried with a decompression device, and then (E)-ethyl 4-(dimethylamino)but-2-enoate hydrochloride of 128.6 g was obtained with a yield of 80%.

Provenance & Evidence