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

Participants

Reaction Conditions

Reaction Steps

Dissolve 2,6-dibromopyridine (5.5 g, 23.2 mmol) in anhydrous dichloromethane (140 mL) under a nitrogen atmosphere. Cool the reaction mixture to −78° C. Add a solution of n-butyl lithium in hexane (1.6 M, 15.8 mL, 25.3 mmol) very slowly via a syringe. After the addition is complete, stir the reaction at −78° C. for 1 hr. Add a solution of 1-methyl-N-methyl-N-methoxy-piperidine-4-carboxamide (2 g, 11 mmol) in anhydrous dichloromethane (10 mL) dropwise to the reaction mixture. Stir the reaction at −78° C. for 2 hrs, and then allow the mixture to slowly warm to room temperature overnight. Quench the reaction with 0.1 N NaOH. Dilute the solution with dichloromethane (100 mL), transfer into a separatory funnel and shake with 2 N NaOH (50 mL). Separate the organic layer, dry it over anhydrous sodium sulfate, and then evaporate the solvent under reduced pressure. Further purify the residue by chromatography on a silica gel column (6%, 2M NH3 in methanol/CH2Cl2) to obtain 2-bromo-6-(1-methylpiperidin-4-ylcarbonyl)-pyridine e (2.3 g, 74% yield). Mass spectrum (ion spray): m/z 283 (M+1).

Provenance & Evidence