Chemical Properties
Off-White Solid
Uses
α,α,α’,α’-Tetramethyl-5-bromomethyl-1,3-benzenediacetonitrile (Anastrozole EP Impurity C) is an impurity of Anastrozole (A637425) (impurity D).
Synthesis
Using 5,α,α,α',α'-pentamethyl-1,3-benzenediacetonitrile as raw material, 3,5-bis(1-cyano-1-methylethyl)toluene (600 g, 2.65 mol) was obtained after step III. The product was mixed with N-bromosuccinimide (519 g, 2.916 mol) and benzoyl peroxide (17 g, 0.053 mol) in carbon tetrachloride (4.5 L) and the reaction was carried out at reflux for 2 to 2.5 hours. After completion of the reaction, the reaction mixture was cooled and filtered. The filtrate was concentrated to dryness at 40°C to 45°C. The resulting solid was dissolved in 2-propanol (2L) at 75°C to 80°C, followed by slow cooling to 10°C to 15°C and stirring at this temperature for 1 hour. The reaction mixture was further cooled to -5 °C to 0 °C and stirring was continued for 2 h, after which it was filtered and the filter cake was washed with pre-cooled 2-propanol (200 ml). The filter cake was subsequently washed with hexane and blotted dry. Finally, the filter cake was dried under vacuum at 40 °C to 45 °C to afford the target product 3,5-bis(1-cyano-1-methylethyl)benzyl bromide (700.2 g, 87.0% yield).
References
[1] Patent: US2006/189670, 2006, A1. Location in patent: Page/Page column 5; 7
[2] Patent: US2006/35950, 2006, A1. Location in patent: Page/Page column 3; 11
[3] Patent: CN103554041, 2016, B. Location in patent: Paragraph 0014-0016
[4] Patent: US2009/221837, 2009, A1. Location in patent: Page/Page column 4
[5] Patent: WO2007/39913, 2007, A1. Location in patent: Page/Page column 14
