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) was 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 2 N aqueous 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 subtitled compound (17 g).

1. customThe flask was purged with nitrogen and azobisisobutyronitrile (0.10 g)
2. additionwas added 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 2 N aqueous 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-9bdb7ac6b7b040e68a57d759dd0df680

Source dataset

uspto-grants-2007_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07297818B2