2,6-Dibromopyridine → (6-Bromopyridin-2-yl)(1-methylpiperidin-4-yl)methanone

Participants

Reaction Conditions

Reaction Steps

Add a solution of n-butyllithium (1.9M in n-hexane, 4 ml, 7.6 mmol) to a solution of 2,6-dibromopyridine (1.81 g, 7.64 mmol) in MTBE (20 mL) dropwise under nitrogen, over 20 min., maintaining the temperature between −72 and −67° C. Stir the yellow heterogeneous solution at −70° C. for 20 min. to provide a green homogeneous solution. Add a solution of 1-methyl-4-(pyrrolidin-1-yl-carbonyl)piperidine (1 g, 5.09 mmol) in 10 mL MTBE dropwise over 20 min., maintaining the temperature below 69° C. Stir the yellow mixture at −75° C. for 1 hr. Quench the reaction mixture with a saturated solution of ammonium chloride (5 mL) between 0 and 10° C. Acidify the mixture to pH 2 with fuming HCl (2 mL). Extract the organic layer. Wash the aqueous phase with MTBE (50 mL), make the aqueous layer basic with a solution of 30% NaOH, and extract with ethyl acetate (2×50 mL). Combine the organic layers, dry over MgSO4, and concentrate under reduced pressure at 40° C. to provide the title intermediate as an oil (1.23 g, 85% yield).

Provenance & Evidence