Tert-Butylamine → Bupropion

Crude 2-bromo-1-(3-chlorophenyl)propan-1-one (2) (152 g, 0.65 mol) was dissolved in 600 ml of acetonitrile (HPLC grade) in a 3-necked 2 L round bottomed flask fitted with a condenser and a dropping funnel. Tert-butylamine (172.5 ml, 1.63 mol) was added drop wise to the resulting mixture, at room temperature and under nitrogen. The reaction mixture was then heated to reflux for approximately 5 hours. During this time the reaction progress was monitored by TLC analysis (silica, hexane: ethyl acetate, 90:10). On consumption of the starting material, the reaction mixture was cooled to room temperature, filtered through celite and the celite washed with approximately 250 ml of ethyl acetate. The filtrate was washed with a 2M solution of KOH (350 ml). The layers were separated and the organic phase was dried over sodium sulphate anhydrous, filtered and concentrated to dryness to give a pale orange oil (147 g, quantitative yield), which did not need any further purification.

1. customfitted with a condenser and a dropping funnel
2. customat room temperature
3. temperatureThe reaction mixture was then heated
4. temperatureto reflux for approximately 5 hours
5. customOn consumption of the starting material
6. filtrationfiltered through celite
7. washthe celite washed with approximately 250 ml of ethyl acetate
8. washThe filtrate was washed with a 2M solution of KOH (350 ml)
9. customThe layers were separated
10. dry with materialthe organic phase was dried over sodium sulphate anhydrous
11. filtrationfiltered
12. concentrationconcentrated to dryness

ORD record

ord-614042db2fca4ac18f8e339d6cb39bfd

Source dataset

uspto-grants-2011_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08030357B2