1001413-01-9

A.1 Dissolve dimethyl 2-(3-methoxyallylidene)malonate (5.00 g, 25.0 mmol) in 40 mL of 2-butanol and cool to 5 °C. 3,4-Difluorobenzylamine (3.00 mL, 25.1 mmol) was dissolved in 10 mL 2-butanol and slowly added to the above solution. The reaction mixture was stirred at 20 °C for 1 h, followed by dilution with 150 mL of 2-butanol and heated to 100 °C and kept for 48 hours. After the reaction was completed, 50 mL of aqueous 2N sodium hydroxide solution and 50 mL of 2N sodium hydroxide methanol solution were added and stirring was continued at 20 °C for 2 hours. The reaction mixture was acidified with 1N HCl (50 mL) and the organic layer was extracted with dichloromethane (3 x 50 mL). The organic layers were combined, dried with anhydrous magnesium sulfate, filtered and the solvent was concentrated in vacuum to give 1-(3,4-difluorobenzyl)-2-oxo-1,2-dihydropyridine-3-carboxylic acid (6.08 g, 90% yield; MS (M + H)+ = 266; tR = 0.00 min; LCMS method: BAS1).

[1] Patent: WO2011/131741, 2011, A1. Location in patent: Page/Page column 54
[2] Patent: WO2011/144622, 2011, A1. Location in patent: Page/Page column 45
[3] Patent: US2012/94976, 2012, A1. Location in patent: Page/Page column 24