Chemical Properties
3,5-Bis(2-cyanoprop-2-yl)toluene is White Solid
Uses
An intermediate in the synthesis of Anastrozole (A637425), an aromatase inhibitor. Used as an antineoplastic.
Uses
α,α,α’,α’-Tetramethyl-5-methyl-1,3-benzenediacetonitrile (Anastrozole EP Impurity H) is an intermediate in the synthesis of Anastrozole (A637425), an aromatase inhibitor. Used as an antineoplastic.
Uses
3,5-Bis(2-cyanoprop-2-yl)toluene is a labelled intermediate in the synthesis of Anastrozole, an aromatase inhibitor. Used as an antineoplastic.
Synthesis
General procedure for the synthesis of 5,α,α,α,α',α'-pentamethyl-1,3-benzenediacetonitrile from 2,2'-(5-methyl-1,3-phenylene)bisacetonitrile and iodomethane: A mixture of 3,5-bis(cyano-methyl)toluene (800 g, 4.70 mol), methyl iodide (2,935.2 g, 20.68 mol) and dimethylformamide (11.20 L) was was cooled to 0°C to 5°C. A dispersion of 60% sodium hydride in mineral oil (864.2 g, 36.0 mol) was added in batches over 1 to 1.5 hours. Subsequently, the reaction mixture was gradually warmed to room temperature and stirred continuously for 2 to 2.5 hours. The progress of the reaction was monitored by thin layer chromatography (TLC, unfolding agent was hexane: ethyl acetate = 7.5:2.5). After confirming the completion of the reaction, ethyl acetate was added to quench the excess sodium hydride. The reaction mixture was diluted with water and extracted with dichloromethane (3 x 5 L). The organic phase was combined and washed with brine (5 L). The organic phase was decolorized with activated charcoal for 1 h at room temperature and subsequently concentrated to dryness under reduced pressure at 40°C to 45°C. The resulting residue was dissolved in carbon tetrachloride (2400 mL) at 70°C to 75°C and gradually cooled to 10°C to 15°C with stirring for 1 hour. The solution was further cooled to -5°C to 0°C and stirring was continued for 3 hours. Finally, the stirred suspension was filtered, the filter cake was washed with pre-cooled carbon tetrachloride (500 mL) and dried under vacuum at 40 °C to 45 °C to give 3,5-bis(1-cyano-1-methylethyl)toluene (748.0 g, 70.3% yield).
References
[1] Organic and Biomolecular Chemistry, 2007, vol. 5, # 18, p. 2940 - 2952
[2] Patent: WO2006/836, 2006, A1. Location in patent: Page/Page column 2; 9-10; 14; Figure 2
[3] Patent: US2006/189670, 2006, A1. Location in patent: Page/Page column 5-7
[4] Patent: WO2007/39913, 2007, A1. Location in patent: Page/Page column 13-14
[5] Patent: US2008/207915, 2008, A1. Location in patent: Page/Page column 5
