Diisopropylamine → 4-Chloropyridine-3-carbaldehyde

Participants

Reaction Conditions

Reaction Steps

35.8 ml of n-BuLi (1.6 M in hexane; 57 mmol, 1 eq.) is added to a solution of 7.5 ml of N,N-diisopropylamine in 100 ml of tetrahydrofuran at −60° C. in nitrogen. The mixture is then left under stirring at 0° C. for 45 min before being cooled to −90° C. To this solution, a solution of 6.5 g of 4-chloropyridine (57 mmol, 1 eq.) in 25 ml of tetrahydrofuran is added drop by drop such that the temperature remains between −70 and −60° C. The mixture is left under stirring at −70° C. for 3 hrs. Then, a solution of 5.1 ml of ethylformate (63 mmol, 1.1 eq.) in 10 ml of tetrahydrofuran is added. The mixture is left under stirring for 1 hr at −65/−70° C. and the reaction mixture is then returned to −10° C. and hydrolysed with water. The organic phase is separated and the aqueous phase is extracted 3 times with ethyl acetate. The combined organic phases are dried on Na2SO4 and the solvent is evaporated.

Provenance & Evidence