5-Chloro-2-fluorobenzyl bromide

Uses

2-(bromomethyl)-4-chloro-1-fluoro-Benzene is a useful reactant which has been used in the synthesis of potential cell cycle inhibitors in HepG2 cells.

Synthesis

General procedure for the synthesis of 5-chloro-2-fluorobenzyl bromide from 5-chloro-2-fluorotoluene: A: 5-Chloro-2-fluorotoluene (100 g, 692 mmol) was dissolved in ethyl acetate (300 ml) at 20 °C. To this solution N-bromosuccinimide (147.7 g, 830 mmol) and dibenzoyl peroxide (2 g, 8.25 mmol) were added sequentially. The reaction mixture was heated to 80 °C and stirred for 3 hours. Upon completion of the reaction, heptane (300 ml) was added and the mixture was cooled to 0 °C, at which time the succinimide precipitated. After filtration and washing with heptane, the residue was washed with water (1500 ml). The filtrate was concentrated to dryness under vacuum to give 162 g of the crude product 5-chloro-2-fluorobenzyl bromide. The crude product (141 g) was purified by vacuum distillation at 99 °C and 33 mbar to give the final 5-chloro-2-fluorobenzyl bromide (99 g, 75% yield). The purity of the product was analyzed by GC to be 87.1% (% area).1H-NMR (CDCl3) data: δ 4.44 (2H, d, CH2), 7.01 (1H, t, H3), 7.26 (1H, m, H4), 7.38 (1H, m, H6).

References

[1] Journal of Heterocyclic Chemistry, 1997, vol. 34, # 1, p. 27 - 32
[2] Patent: WO2008/3460, 2008, A1. Location in patent: Page/Page column 23-24
[3] Patent: US2008/9619, 2008, A1. Location in patent: Page/Page column 11-12
[4] Journal of Medicinal Chemistry, 1991, vol. 34, # 10, p. 3098 - 3105
[5] Journal of the Chemical Society - Perkin Transactions 1, 1997, # 19, p. 2903 - 2909