N-bromobutanimide → 5-(Bromomethyl)-2-chlorobenzoic acid

To a stirred solution of 2-chloro-5-methyl-benzoic acid (25 g) in chloroform (500 ml) at 50° C. was added N-bromosuccinimide (27.40 g). The flask was purged with nitrogen and azobisisobutyronitrile (0.10 g) added in one portion. The solution was heated at reflux for 1 h. Further azobisisobutyronitrile (0.10 g) was added and the mixture heated a further 3 h. The solution was concentrated in vacuo, redissolved in diethyl ether and filtered to remove insoluble succinimide. The ether solution was washed with 2N aqueos hydrochloric acid solution followed by brine then dried over magnesium sulphate. The solution was concentrated to a volume of 150 ml then diluted with isohexane. After further partial concentration crystallization started. The mixture was allowed to stand in an ice-bath for 1 h. The resulting crystals were filtered, washed with isohexane and dried in vacuo to give the subtitle compound (17 g).

1. customThe flask was purged with nitrogen and azobisisobutyronitrile (0.10 g)
2. additionadded in one portion
3. temperatureThe solution was heated
4. temperatureat reflux for 1 h
5. additionFurther azobisisobutyronitrile (0.10 g) was added
6. temperaturethe mixture heated a further 3 h
7. concentrationThe solution was concentrated in vacuo
8. dissolutionredissolved in diethyl ether
9. filtrationfiltered
10. customto remove insoluble succinimide
11. washThe ether solution was washed with 2N aqueos hydrochloric acid solution
12. dry with materialthen dried over magnesium sulphate
13. concentrationThe solution was concentrated to a volume of 150 ml
14. additionthen diluted with isohexane
15. concentrationAfter further partial concentration crystallization
16. filtrationThe resulting crystals were filtered
17. washwashed with isohexane
18. customdried in vacuo

ORD record

ord-9467340f6fbc43a2b036beac342969d9

Source dataset

uspto-grants-2002_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06492355B1