Dimethylformamide → 6-Chloro-4-formylpyridine-3-carboxylic acid

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of tetramethylpiperidine (6.89 mL, 40.8 mM) in dry tetrahydrofuran (20 mL), n-butyl lithium (36.5 mL, 1.12 mL, 40.8 mM) was added drop wise at −78° C. for 15 min. The reaction mixture was stirred at −78° C. for 30 min and at −50° C. for 30 min. 6-Chloro nicotinic acid (1.6 g, 10.2 mM) dissolved in dry tetrahydrofuran (10 mL) was added dropwise to the above reaction mixture for 15 min at −78° C. The reaction mixture was stirred at −78° C. for 30 min and at −50° C. for 30 min. Dry dimethyl formamide (5 mL) was added dropwise at −78° C. for 5 min. The reaction mixture was stirred at −78° C. for 30 min and at −50° C. for 30 min. After the completion of the reaction, reaction mixture was quenched with 2N hydrochloric (30 mL) extracted with ethyl acetate (2×150 mL). Organic layer dried over anhydrous MgSO4, then concentrated. The concentrate was subjected to column chromatography, and the product was eluted with 15% ethyl acetate in petroleum ether to get 1.01 g (53.19%) of the title compound. MS (APCI): 186 (M+H+) for C7H4ClNO3; NMR CD3OD): δ 6.18 (s, 1H), δ 7.75 (s, 1H), δ 8.74 (s, 1H).

Provenance & Evidence