Methyl iodide → 5-bromo-1,3-difluoro-2-methylbenzene

To a solution of 2.04 g of diisopropylamine in 30 ml of tetrahydrofuran is dropwise added 9.19 ml of 1.6 M n-hexane solution of n-butyllithium at -20° C. At the same temperature, the resulting mixture is stirred for one hour and then cooled to -70° C., at which temperature a solution of 3 g of 3,5-difluorobromobenzene in 10 ml of tetrahydrofuran is dropwise added thereto over 30 minutes. The temperature of the resulting reaction mixture is elevated to -40° C. and then lowered again to -70° C., at which temperature 0.97 ml of methyl iodide is then added thereto. The temperature of the resulting mixture is elevated to room temperature, and 80 ml of water and 80 ml of ethyl acetate are then added thereto, after which the resulting organic layer is separated, washed successively with water and a saturated saline solution and then dried over anhydrous magnesium sulfate. Thereafter, the solvent is removed from the thus dried layer by distillation under reduced pressure. The residue obtained is purified by a column chromatography [eluent:hexane:ethyl acetate=10:1], to obtain 1.98 g of colorless, oily 4-bromo-2,6-difluorotoluene.

1. customat -20° C
2. additionis dropwise added
3. waitover 30 minutes
4. customThe temperature of the resulting reaction mixture
5. customis elevated to -40° C.
6. additionis then added
7. customis elevated to room temperature
8. customafter which the resulting organic layer is separated
9. washwashed successively with water
10. dry with materiala saturated saline solution and then dried over anhydrous magnesium sulfate
11. customThereafter, the solvent is removed from the thus dried layer by distillation under reduced pressure
12. customThe residue obtained
13. customis purified by a column chromatography [eluent:hexane:ethyl acetate=10:1]

ORD record

ord-e3b3ae8f1ef247bb9cefe4c9f4d1c34e

Source dataset

uspto-grants-1999_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05968935