Dimethylamine → (E)-4-dimethylamino Crotonate Hydrochloride

Temperature

-10 °C

(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%.

1. additionwas slowly added as droplets into the flask for 1 hour
2. temperatureAt this time, the internal temperature of the reactor was maintained
3. customto be 5° C. or less
4. additionwas added
5. stirringthe mixture was stirred until the starting materials
6. customabout 30 minutes and it
7. customdid not get long
8. customThe reaction mixture was separated
9. dry with materialThe separated organic layer was dried with anhydrous MgSO4
10. filtrationfiltered
11. concentrationconcentrated
12. dissolutionwas dissolved
13. additionwas slowly added as droplets
14. customfell down to room temperature
15. filtrationthe reaction mixture was filtered with
16. filtrationa filter
17. waitthe solid left in the filter
18. washwas washed with EtOAc (500 mL)
19. customThe solid was transferred into one-neck flask
20. customdried with a decompression device

ORD record

ord-69326cc048cd4f2683d0fb3386a0b5b5

Source dataset

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08779192B2