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Example 74 Synthesis of ethyl 4-amino-5-cyano-2-hydroxy-3-methylbenzoate (74): ethyl propionylacetate (25 g, 0.17 mol) was slowly added to a freshly prepared sodium ethanol solution (prepared by reacting sodium metal (7.9 g, 0.35 mol) with ethanol (1.3 L)) at 0 °C, followed by stirring the reaction mixture for 1 hour at room temperature. Next, ethoxymethylene malononitrile (21 g, 0.17 mol) was added to the above reaction system at room temperature and the reaction mixture was warmed up to 80°C and refluxed for 2 hours. Upon completion of the reaction, the mixture was cooled to room temperature, neutralized to pH=7 with 1.5N HCl solution and subsequently concentrated under vacuum. The concentrated residue was diluted with 100 mL of water and the solid product was collected by filtration. The solid product was washed with water and dried under vacuum at 50 °C to give a crude product of 27 g. The crude product was further purified by washing with petroleum ether containing 5% ethyl acetate to give a final pure title compound of 22.5 g in 59% yield.

[1] Patent: US2009/118312, 2009, A1. Location in patent: Page/Page column 52
[2] Liebigs Annalen der Chemie, 1979, p. 2005 - 2010