Synthesis
(b) Synthesis of 4-amino-2-methylbenzonitrile: Tin chloride dihydrate (18.5 g, 82.0 mmol) was added to a solution of 2-methyl-4-nitrobenzonitrile (3.80 g, 23.4 mmol) in ethanol (140 mL). The reaction mixture was stirred under reflux conditions for 3 hours. After completion of the reaction, the solvent was removed by distillation. The residue was diluted with ethyl acetate and washed with saturated aqueous sodium bicarbonate solution. The precipitate produced during washing was removed by filtration through diatomaceous earth. The filtrate was extracted with ethyl acetate and the combined organic phases were dried with anhydrous magnesium sulfate, filtered and concentrated to give 4-amino-2-methylbenzonitrile (2.89 g, 94% yield).
References
[1] Patent: EP1500643, 2005, A1. Location in patent: Page 32
[2] Chemische Berichte, 1919, vol. 52, p. 1083
[3] Journal of Organic Chemistry, 1962, vol. 27, p. 1426 - 1430
[4] Journal of Medicinal Chemistry, 2001, vol. 44, # 23, p. 3856 - 3871
[5] Bioorganic and Medicinal Chemistry Letters, 2008, vol. 18, # 6, p. 1926 - 1930
