2,4-Dichloropyridine-3-carboxaldehyde

2,4-Dichloronicotinaldehyde, also known as 2,4-dichloronicotinaldehyde, can be obtained by reacting 2,4-dichloropyridine with a strong base to obtain (2,4-4-dichloro-3-pyridyl)lithium, and then reacting it with DMF.

Yellow solid

To a solution of 2,4-dichloropyridine (2 g, 13.51 mmol) in tetrahydrofuran (20 mL) at -78° C added LDA in THF/heptane/ethylbenzene (2M, 8.11 mL, 16.22 mmol) and the solution was stirred for 30 min. DMF (10.46 mL, 135 mmol) was added and the solution was stirred for 1 h and then warmed RT. The reaction mixture was quenched with saturated NH4Cl solution and diluted with ethyl acetate (50 mL). The organic layer was washed with saturated NaHCO3 (2*10 mL), water (20 mL), dried over Na2SO4, and concentrated under reduced pressure to afford 2,4-dichloronicotinaldehyde (2 g, 11.36 mmol, 84% yield). 

[1] Tetrahedron Letters, 2011, vol. 52, # 4, p. 523 - 525
[2] Organic Process Research and Development, 2018, vol. 22, # 8, p. 978 - 990
[3] Patent: US2013/237555, 2013, A1. Location in patent: Paragraph 0273
[4] Patent: WO2015/38112, 2015, A1. Location in patent: Page/Page column 126
[5] Patent: WO2018/109050, 2018, A1. Location in patent: Paragraph 0286-0297