Hydrogen Bromide → 5-Bromo-1,3-dichloro-2-methylbenzene

Suspend 3,5-dichloro-4-methylaniline in 48% HBr (5 mL) and water (5 mL) and heat with a heat gun until the mixture is near the boiling point. Cool the slurry to room temperature and then cool to 0° C. with an ice/brine bath. Add dropwise a solution of sodium nitrite (109 mg, 1.58 mmol) in water (2 mL). After the addition is complete, stir the reaction an additional 15 min in the cold bath. Add a solution of CuBr (1.08 g, 7.53 mmol) in 48% HBr (2 mL) and heat the rapidly stirring reaction to 50° C. for 1 hour. Cool the reaction to room temperature, dilute with EtOAc and discard the aqueous layer. Wash the organic layer with water and brine, dry with MgSO4, filter through celite and concentrate to an orange residue. Purify the residue by silica gel chromatography eluting with hexanes to afford 164 mg (45%) of the product as a yellow solid.

1. temperatureheat with a heat gun until the mixture
2. temperaturecool to 0° C. with an ice/brine bath
3. additionAfter the addition
4. customthe reaction an additional 15 min in the cold bath
5. temperatureheat the
6. stirringrapidly stirring
7. customreaction to 50° C. for 1 hour
8. temperatureCool
9. customthe reaction to room temperature
10. washWash the organic layer with water and brine
11. dry with materialdry with MgSO4
12. filtrationfilter through celite
13. concentrationconcentrate to an orange residue
14. customPurify the residue by silica gel chromatography
15. washeluting with hexanes

ORD record

ord-c159d6a41741433ebf97aa3d280c2207

Source dataset

uspto-grants-2011_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07994176B2