Step 3 Synthesis of 1-(6-chloropyridin-3-yl)ethanone: Dimethyl 2-(6-chloronicotinoyl)malonate (89.8 g, 331 mmol) was dissolved in a solvent mixture of DMSO (445 mL) and water (11 mL), and the reaction was heated for 2.5 hr at 130 °C. After the reaction was completed, the reaction mixture was cooled and poured into H2O/ice (300 mL). The aqueous phase was extracted with EtOAc (4 x 150 mL). The organic phases were combined, washed with brine, dried and concentrated under reduced pressure. The residue was recrystallized by 60% ethanol-water solution to afford the target compound 1-(6-chloropyridin-3-yl)ethanone in a yield of 16.5 g (32% yield) as a yellow solid.
[1] Bioorganic and Medicinal Chemistry Letters, 2008, vol. 18, # 23, p. 6093 - 6096
[2] Bioorganic and Medicinal Chemistry Letters, 2008, vol. 18, # 24, p. 6482 - 6485
[3] Patent: US2007/27184, 2007, A1. Location in patent: Page/Page column 17; 19
[4] Tetrahedron, 1992, vol. 48, # 42, p. 9233 - 9236
[5] Bioorganic and Medicinal Chemistry Letters, 2003, vol. 13, # 18, p. 3041 - 3044
