Dimethylformamide → 6-Chloro-3-Methylpicolinaldehyde

Participants

Reaction Steps

2-Bromo-6-chloro-3-methyl-pyridine was prepared from 2-chloro-5-methylpyridine by by the method of Gros P. and Fort Y. (J. Org. Chem., 2005, 8220). A solution of n-BuLi (1.6M in hexanes) (2.0 ml, 3.30 mmol) in dry THF (6 ml) at −78° C. under argon was treated dropwise with a solution of 2-bromo-6-chloro-3-methyl-pyridine (642 mg, 3.10 mmol) in dry THF (4 ml) and stirred at this temperature for 30 minutes. A solution of DMF (385 μl, 4.70 mmol) in dry THF (1 ml) was added dropwise and stirred at −78° C. for a further 45 minutes before warming to ambient temperature. The reaction was quenched with MeOH (3 ml), treated with water and extracted with EtOAc. The combined organics were dried over MgSO4, filtered and evaporated under reduced pressure before purification by column chromatography on SiO2, eluting with 2% EtOH in DCM to afford 6-chloro-3-methyl-pyridine-2-carbaldehyde as a yellow solid (217 mg, 45%). 1H NMR (400 MHz, CDCl3) δ 10.09 (s, 1H), 7.60 (d, J=7.7 Hz, 1H), 7.42 (d, J=7.7 Hz, 1H), 2.64 (s, 3H).

Provenance & Evidence