Reacción #45293

Ecuación de reacción

t-Butylamine

m-chloro-α-bromopropiophenone

→

compound III

bupropion

Condiciones de reacción

Tratamiento posterior

1. 1
   Otroobtained above and the reaction mixture
2. 2
   Temperaturawas refluxed for 5.5 hours
3. 3
   OtroAfter excessive t-butylamine was evaporated below 100° C.
4. 4
   Extracciónextracted with 1000 ml of toluene and 200 ml of water
5. 5
   SecadoThe organic phase was dried with anhydrous magnesium sulfate (20 g)

Procedimiento

To 1 mole of m-chloroprophenone heated to 75±5° C., bromine was added dropwise under stirring, and the reaction temperature was kept at 75±5° C. during the addition and kept for 3 hours after the addition, m-chloro-α-bromopropiophenone (compound of formula (II)) was obtained. t-Butylamine was added to m-chloro-α-bromopropiophenone obtained above and the reaction mixture was refluxed for 5.5 hours. After excessive t-butylamine was evaporated below 100° C., the concentrated solution was cooled down to room temperature and then extracted with 1000 ml of toluene and 200 ml of water. The organic phase was dried with anhydrous magnesium sulfate (20 g) to obtain a solution of bupropion free base (compound III). HCl gas was bubbled into the solution of bupropion free base at room temperature until the PH value the reaction mixture was less than or equal to 4. After filtration, crude product of bupropion hydrochloride was obtained. The crude product of bupropion hydrochloride was dissolved in 1500 ml of ethyl acetate heated to 60° C., and decolorized with activated carbon (3 g) for 30 minutes and filtered. Then filtrate was cooled down, crystal bupropion hydrochloride crystallized. Wet product of bupropion hydrochloride was obtained after filtration and was dried in vacuum (−0.04˜−0.09 MPa, 60±5° C.) for 5 hours to obtain pure product. Total yields was 75% based on m-chloropropiophenone; HPLC's purify was over 99.9%.

Fuente