反应详情

Charge 2-bromo-1-[3(trifluoromethyl)phenyl]-1-ethanone (1664.7 g; 1.00 equiv; 6.23 moles) and tetrahydrofuran (7500 mL) to a 12 L 3-necked round bottom flask (fitted with water-cooled condenser, nitrogen blanket, mechanical stirrer and cooling bath. Charge sodium azide (425.6 g; 1.05 equiv; 6.55 moles) in one portion. Rinse into the flask with water (135 mL). Stir the pale yellow slurry at RT under nitrogen. After 6 hours, add water (260 mL) and continue to stir overnight. Filter the resulting orange slurry over a thin pad of Celite® and rinse with THF (1 L). Divide the resulting solution into two equal portions (5146.5 g each). Charge two identical 22 L 3-necked round bottom flask (fitted with addition funnel, water-cooled condenser, nitrogen blanket, mechanical stirrer and cooling bath) with triphenylphosphine (889 g, 3.43 mol, 1.1 eq), p-toluenesulfonic acid monohydrate (1304 g, 6.86 mol, 2.2 eq) and THF (5.6 L). Add the two portions of intermediate mixture via addition funnels to the individual flasks over four hours, controlling the foaming from nitrogen evolution by addition rate and the temperature by use of an ice bath. On completion of addition stir the slurry at ambient temperature for two hours, then filter solids from both reactors onto the same filter. Wash both flasks and the combined cake with a total THF (4 L). Dry in a vacuum oven at 40° C. overnight to afford (2-Amino-1-(3-trifluoromethyl-phenyl)-ethanone)-, p-toluene sulfonate (1:1) as a white, crystalline solid (2340 g, 6.23 mol, 72%).

1. temperaturecooled condenser
2. temperaturenitrogen blanket, mechanical stirrer and cooling bath
3. washRinse into the flask with water (135 mL)
4. additionadd water (260 mL)
5. stirringto stir overnight
6. filtrationFilter the resulting orange slurry over a thin pad of Celite®
7. washrinse with THF (1 L)
8. additionCharge
9. additionAdd the two portions of intermediate mixture
10. additionvia addition funnels to the individual flasks over four hours
11. additionby addition rate
12. additionOn completion of addition
13. stirringstir the slurry at ambient temperature for two hours
14. filtrationfilter solids from both reactors onto the same filter
15. washWash both flasks
16. customDry in a vacuum oven at 40° C. overnight