Hydrogen Bromide → HCID 13553298, compound

Temperature

15 °C

A 5 1, 3-necked round-bottom flask, equipped with an overhead stirrer, thermometer and addition funnel was charged with 2-bromo-4,6-dimethylaniline hydrobromide (713 g, 2.54 mol) and acetone (1.9 1). The slurry was cooled to 15° C. and 48% aqueous hydrobromic acid (450 ml, 4.0 mol), was added. The mixture was cooled to -4° C. then a solution of sodium nitrite (219 g, 3.17 mol) in 400 ml of water was slowly added with vigorous stirring while maintaining an internal temperature of 0° C. Acrylonitrile (550 ml) was charged and the reaction mixture was degassed under vacuum then purged with nitrogen. Cuprous bromide (3.0 g, 0.021 mol) was charged and the mixture stirred with gradual warming to ambient temperature over 6 hours. The mixture was aged with stirring, for 6 additional hours. The mixture was concentrated under vacuum, collecting 3 1 of solvent. The residue was diluted with toluene (3 1), the organic extract was washed with 3×500 ml of water, dried over sodium sulfate, filtered, and concentrated to a volume of 1 1. The dark concentrate was charged with triethylamine (1.2 1) and heated at 80°-90° C. under nitrogen for 6.5 hours. The mixture was concentrated under vacuum to a thick slurry then diluted with toluene (2.5 1). The organic phase was extracted 2×500 ml with 3 N aqueous hydrochloric acid, 2×500 ml with water, then dried over sodium sulfate. After filtration the toluene extract was treated with activated charcoal (10 g) at ambient temperature then filtered through super-cel. Removal of the solvent in vacuo yielded a yellow oil which solidified on standing. The crude nitrile was dissolved in a solution of cyclohexane (525 ml) and hexanes (840 ml) with heating. The mixture was gradually cooled to 3° C., filtered, washed with 500 ml of cold hexane and dried in vacuo to yield the Compound 2a as a light yellow solid (mp 95°-96° C.). The crystallization mother liquors contained an additional product.

1. customA 5 1, 3-necked round-bottom flask, equipped with an overhead stirrer
2. additionthermometer and addition funnel
3. temperatureThe mixture was cooled to -4° C.
4. temperaturewhile maintaining an internal temperature of 0° C
5. customthe reaction mixture was degassed under vacuum
6. customthen purged with nitrogen
7. stirringthe mixture stirred
8. temperaturewith gradual warming to ambient temperature over 6 hours
9. stirringwith stirring, for 6 additional hours
10. concentrationThe mixture was concentrated under vacuum
11. customcollecting 3 1 of solvent
12. additionThe residue was diluted with toluene (3 1)
13. extractionthe organic extract
14. washwas washed with 3×500 ml of water
15. dry with materialdried over sodium sulfate
16. filtrationfiltered
17. concentrationconcentrated to a volume of 1 1
18. concentrationThe dark concentrate
19. additionwas charged with triethylamine (1.2 1)
20. temperatureheated at 80°-90° C. under nitrogen for 6.5 hours
21. concentrationThe mixture was concentrated under vacuum to a thick slurry
22. additionthen diluted with toluene (2.5 1)
23. extractionThe organic phase was extracted 2×500 ml with 3 N aqueous hydrochloric acid, 2×500 ml with water
24. dry with materialdried over sodium sulfate
25. filtrationAfter filtration the toluene
26. extractionextract
27. additionwas treated with activated charcoal (10 g) at ambient temperature
28. filtrationthen filtered through super-cel
29. customRemoval of the solvent in vacuo
30. customyielded a yellow oil which
31. temperaturewith heating
32. temperatureThe mixture was gradually cooled to 3° C.
33. filtrationfiltered
34. washwashed with 500 ml of cold hexane
35. customdried in vacuo

ORD record

ord-d0ce394662b24857a5d88d800aa437ef

Source dataset

uspto-grants-1986_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04620025