(E)-4二甲胺巴豆酸乙酯盐酸盐

反应条件: temp:45.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: (E)-ethyl 4-(dimethylamino)but-2-enoate hydrochloride (20 g, 0.103 mol) was dissolved in water (102 mL) in 250 mL two-neck flask, and then conc. HCl (2.6 mL) was added therein. After refluxing the reaction mixture for 3 hours, the temperature of the reaction mixture was reduced to room temperature. EtOH formed in the reaction was eliminated by distillation under reduced pressure, and then water (34 mL) was added therein. After adding conc. HCl (1.3 mL) therein again, the reaction mixture was refluxed again for 2 hours and water in the reaction mixture was eliminated by distillation under reduced pressure. Re-crystallization was carried out by adding IPA (100 mL) to the solid remained therein. At this time, IPA solution was heated to the temperature of 40 to 50° C., and the solution was stirred for 2 hours at room temperature. After filtering the solid with a filter, the solid was washed with IPA (10 mL). (E)-4-(dimethylamino) but-2-enoic acid hydrochloride of 12 g was obtained with a yield of 70% by drying the collected solid (99.8% Purity by HPLC, Corona Detector). After refluxing the reaction mixture for 3 hours was reduced to room temperature was eliminated by distillation under reduced pressure water (34 mL) was added After adding conc. HCl (1.3 mL) again, the reaction mixture was refluxed again for 2 hours water in the reaction mixture was eliminated by distillation under reduced pressure by adding IPA (100 mL) to the solid After filtering the solid with a filter the solid was washed with IPA (10 mL)

反应条件: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: (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%. 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 was added the mixture was stirred until the starting materials about 30 minutes and it did not get long The reaction mixture was separated The separated organic layer was dried with anhydrous MgSO4 filtered concentrated was dissolved was slowly added as droplets fell down to room temperature the reaction mixture was filtered with a filter the solid left in the filter was washed with EtOAc (500 mL) The solid was transferred into one-neck flask dried with a decompression device