1083057-14-0

The general procedure for the synthesis of tert-butyl 3-(6-amino-3-methylpyridin-2-yl)benzoate from 2-(3-(tert-butoxycarbonyl)phenyl)-3-methylpyridine-1-oxide is as follows: a mixture of 2-(3-(tert-butoxycarbonyl)phenyl)-3-methylpyridine-1-oxide (1 eq.) and pyridine (4 eq.) in acetonitrile (8 vol.) was heated to 70 °C. A solution of methylsulfonic anhydride (1.5 eq.) in acetonitrile (2 vol.) was slowly added through the addition funnel over 50 min, and the reaction temperature was controlled below 75 °C. After the addition was completed, stirring of the reaction mixture was continued for 0.5 hours. The reaction mixture was then cooled to room temperature. Ethanolamine (10 equivalents) was added through the addition funnel and after stirring the reaction for 2 hours, water (6 volumes) was added and the mixture was cooled to 10°C. After continued stirring for not less than 3 hours, the solid product was collected by filtration. The solid was washed sequentially with water (3 volumes), a 2:1 acetonitrile/water mixture (3 volumes) and acetonitrile (2 x 1.5 volumes). The solid was dried in a vacuum oven at 50 °C to constant weight (less than 1% change in weight) and kept under a slight stream of nitrogen to give tert-butyl 3-(6-amino-3-methylpyridin-2-yl)benzoate as a reddish yellow solid in 53% yield.

[1] Patent: WO2009/76142, 2009, A2. Location in patent: Page/Page column 54
[2] Patent: WO2009/73757, 2009, A1. Location in patent: Page/Page column 23
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