反应详情

(S)-2-methyl-1-phenyl-2-(pyridine-2-yl)propan-1-amine (821.7 g, 3.63 moles) was dissolved in methanol (5000 mL) giving a reddish-orange solution. The solution was treated with Norit decolorizing Carbon (50 g) and stirred at gentle reflux for 2 hours. The hot solution was filtered through a pad of Celite, giving a light yellow filtrate. The Carbon filter cake was further washed with hot methanol (2×1000 mL), and the washes combined with the original filtrate. The decolorized solution of (4) was treated with fumaric acid (421.4 g, 3.63 moles), added as a dry solid over a period of 5 minutes. The solution was allowed to stir at room temperature for 30 minutes, then was concentrated under reduced pressure to remove most of the methanol (6000 mL removed). The resulting thick amber syrup was diluted gradually with vigorous stirring with diethyl ether (7000 mL) until crystallization ensued. The mixture was stirred vigorously until a very healthy crop of crystals had formed. The mixture was then further diluted with additional diethyl ether (2000 mL, total volume of 9000 mL) with vigorous stirring to complete the crystallization. The crystals were collected by suction filtration and pulled free of liquors. The crystals were re-suspended in a mixture of 9:1 diethyl ether/methanol (2000 mL) and stirred vigorously for several minutes, then re-filtered and pulled dry. The process was repeated a second time. The white crystals obtained from this treatment were dried to constant weight in the vacuum oven at 60° C. to yield (S)-2-methyl-1-phenyl-2-(pyridine-2-yl)propan-1-amine fumarate salt (1179.3 g, 95% yield). 1H NMR (300 MHz, DMSO-d 6) δ ppm 9.19 (br. s., 3 H) 8.62 (d, J=3.37 Hz, 1 H) 7.71 (td, J=7.80, 1.69 Hz, 1 H) 7.17-7.39 (m, 5 H) 6.94-7.17 (m, 2 H) 6.51 (s, 2 H) 4.64 (s, 1 H) 1.35 (s, 3 H) 1.26 (s, 3 H). 13C NMR (75 MHz, DMSO-d 6): δ ppm 23.7, 25.7, 43.8, 62.7, 121.3, 122.3, 128.0, 128.1, 128.6, 135.5, 137.4, 137.8, 148.7, 164.9, 168.3. MS: m/z 227.

1. customgiving a reddish-orange solution
2. temperatureat gentle reflux for 2 hours
3. filtrationThe hot solution was filtered through a pad of Celite
4. customgiving a light yellow filtrate
5. filtrationThe Carbon filter cake
6. washwas further washed with hot methanol (2×1000 mL)
7. additionadded as a dry solid over a period of 5 minutes
8. stirringto stir at room temperature for 30 minutes
9. concentrationwas concentrated under reduced pressure
10. customto remove most of the methanol (6000 mL removed)
11. additionThe resulting thick amber syrup was diluted gradually
12. stirringwith vigorous stirring with diethyl ether (7000 mL) until crystallization
13. stirringThe mixture was stirred vigorously until a very healthy crop of crystals
14. customhad formed
15. stirringwith vigorous stirring
16. customthe crystallization
17. filtrationThe crystals were collected by suction filtration
18. additionThe crystals were re-suspended in a mixture of 9:1 diethyl ether/methanol (2000 mL)
19. stirringstirred vigorously for several minutes
20. filtrationre-filtered
21. custompulled dry
22. customThe white crystals obtained from this treatment
23. customwere dried to constant weight in the vacuum oven at 60° C.