Synthesis
(A) Synthesis of methyl 2,6-dichloro-4-methylnicotinate: 8.05 g (39.1 mmol) of 2,6-dichloro-4-methylnicotinate [Lamm, G. Ger. Offen. (1977), DE 2538950] was dissolved in 100 mL of DMF, followed by the addition of 8.10 g (58.6 mmol) of potassium carbonate. Under stirring conditions, 12.16 mL (27.7 g, 195.4 mmol) of iodomethane was added slowly and dropwise. The reaction mixture was stirred continuously for 6 hours at room temperature. After completion of the reaction, the mixture was poured into crushed ice and extracted twice with EtOAc. The organic phases were combined, washed with water, dried over magnesium sulfate, filtered and the solvent evaporated to give 8.47 g (99% yield) of methyl 2,6-dichloro-4-methylnicotinate as a light yellow solid. Mass spectral data: 219.0 (M+, containing 2Cl).
References
[1] Patent: US2009/48238, 2009, A1. Location in patent: Page/Page column 22
[2] Patent: US2009/318467, 2009, A1. Location in patent: Page/Page column 23
[3] Patent: US2012/101079, 2012, A1. Location in patent: Page/Page column 74
[4] Patent: WO2012/52167, 2012, A1. Location in patent: Page/Page column 171-172
[5] Patent: US2017/183342, 2017, A1. Location in patent: Paragraph 0231
