反应详情

To a solution of 3,3-dimethylbutanal (9.90 g, 99 mmol) in acetonitrile (60 mL) were added molecular sieves (8 g) and (R)-(tetrahydrofuran-2-yl)methanamine (10 g, 99 mmol). The reaction mixture was stirred at room temperature for 24 hours and then filtered through celite. To the filtrate was added potassium thiocyanate (12.78 g, 131 mmol). The temperature was adjusted to 50° C. and the mixture was stirred until the solids were dissolved. Then, iodine (25.09 g, 99 mmol) was added to the mixture and stirred at 50° C. for 24 hours. The reaction mixture was cooled, and to the mixture was added sodium meta-bisulfite 20% (100 mL) and stirred for 30 min. The organic layers were separated and the aqueous layer was washed with dichloromethane (3×40 mL). The combined organic extracts were dried with sodium sulfate, filtered and concentrated to obtain the crude product as a yellow solid. The residue was taken into dichloromethane (20 mL) and ethyl acetate (80 mL), the mixture was warmed to 40° C., sonicated, and cooled to between 0-10° C. The solid was collected and washed with cold ethyl acetate to obtain the title compound (18.2 g, 50%). 1H NMR (300 MHz, DMSO-d6) δ ppm 1.27 (s, 9 H) 1.48-1.61 (m, 1 H) 1.78-1.93 (m, 2 H) 1.94-2.07 (m, 1 H) 3.62-3.71 (m, 1 H) 3.76-3.84 (m, 1 H) 3.92-4.08 (m, 2 H) 4.11-4.20 (m, 1 H) 7.19 (s, 1 H) 9.39 (s, 2 H); MS (DCI/NH3) m/z 241 (M+H)+.

1. filtrationfiltered through celite
2. customwas adjusted to 50° C.
3. stirringthe mixture was stirred until the solids
4. dissolutionwere dissolved
5. stirringstirred at 50° C. for 24 hours
6. temperatureThe reaction mixture was cooled
7. stirringstirred for 30 min
8. customThe organic layers were separated
9. washthe aqueous layer was washed with dichloromethane (3×40 mL)
10. dry with materialThe combined organic extracts were dried with sodium sulfate
11. filtrationfiltered
12. concentrationconcentrated
13. customto obtain the crude product as a yellow solid
14. temperaturethe mixture was warmed to 40° C.
15. customsonicated
16. temperaturecooled to between 0-10° C
17. customThe solid was collected
18. washwashed with cold ethyl acetate