Water → 1-(2-amino-5-bromophenyl)-propan-1-one

Temperature

-10 °C

A three-necked round bottom flask under N2 was charged with AlCl3 (775 mg, 5.81 mmol), then add 5.00 mL of toluene. The slurry was cooled to −10° C. and 4-bromoaniline (1.0 g, 5.81 mmol) was added in one portion. To this was added BCl3 (6.4 mL of 1.0 M solution in xylene) to the mixture at −10° C. slowly, and the mixture was purged with N2 until no more smoke appeared. Propioitrile (1.88 mL, 25.6 mmol) was added and the temperature was allowed to raise to no great than 45° C. The reaction was heated at 63° C. for 10 minutes and maintained at 63° C. for 5 minutes to give a homogeneous solution. Another 4.0 mL of toluene was added into another three-necked flask, and heated to reflux under N2. The solution from previous flask was added to the toluene at reflux over 10 minutes. The mixture was heated to reflux for an additional 4 hours, while continuing to purge the reaction with N2. Toluene would be lost during this process, added more toluene to the mixture if necessary. The reaction was cooled to room temperature and 10 mL of water was added under efficient stirring for ˜30 minutes. The mixture was heated to 55° C. and stirred for 15 minutes before allowing separation into two layers. The organic phase was washed with water, dried over MgSO4, filtered, and concentrated to give a crude solid. The residue was purified though column chromatography (0-50% EtOAc/Heptane gradient) to afford 1-(2-amino-5-bromophenyl)-propan-1-one as a yellow solid (144.0 mg, 10.9%).

1. customthe mixture was purged with N2 until no more smoke
2. additionPropioitrile (1.88 mL, 25.6 mmol) was added
3. temperatureto raise to no great than 45° C
4. temperatureThe reaction was heated at 63° C. for 10 minutes
5. temperaturemaintained at 63° C. for 5 minutes
6. customto give a homogeneous solution
7. temperatureheated
8. temperatureto reflux under N2
9. temperatureat reflux over 10 minutes
10. temperatureThe mixture was heated
11. temperatureto reflux for an additional 4 hours
12. customto purge
13. customthe reaction with N2
14. temperatureThe reaction was cooled to room temperature
15. temperatureThe mixture was heated to 55° C.
16. stirringstirred for 15 minutes
17. customseparation into two layers
18. washThe organic phase was washed with water
19. dry with materialdried over MgSO4
20. filtrationfiltered
21. concentrationconcentrated
22. customto give a crude solid
23. customThe residue was purified though column chromatography (0-50% EtOAc/Heptane gradient)

ORD record

ord-7efb04328a8849f5907aa88509cea937

Source dataset

uspto-grants-2012_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08318762B2