Methanol → 6-Chloropyridine-3-carbaldehyde

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Reaction Conditions

Reaction Steps

In a dry 50 ml flask 2.47 g (10.3 mmole) 2-chloro-5-iodo-pyridine was dissolved in 20 ml of dry diethyl ether. The flask was placed under N2-atmosphere, cooled to −78° C. and 5.1 ml of a 2M solution (10.3 mmole) butyl lithium (BuLi) was added. The reaction mixture was stirred for one hour at −78° C. before adding 1 g (4.1 mmole) of the nitrile compound of example 7. Stirring was continued for 30 minutes at −78° C. and the reaction mixture was then allowed to slowly warm up to room temperature. After 16 hours at room temperature methanol was added in order to neutralise the excess BuLi, and the volatile components were evaporated. The reaction mixture was redissolved in 25 ml of a 1:1 mixture of methanol and 0.5M HCl. 0.5 g of silica gel was added and the mixture was stirred for 15 hours at room temperature. The pH was adjusted to approximately 8 by adding a concentrated NaHCO3 solution. The resulting reaction product was extracted three times by means of dichloromethane and the combined organic phases were dried over MgSO4. After filtration of the solids and evaporation of the volatile components, purification was performed by means of column chromatography, and any remaining 2-chloropyridine was removed by sublimation under high vacuum conditions. 7-(4-methoxybenzyl)-7-azabicyclo[2.2.1]hept-1-yl)-(6-chloro-pyridin-3-yl)-methanone was obtained in a 62% yield and characterised by proton (1H-NMR) and carbon (13C-NMR) nuclear magnetic resonance, infrared (IR) spectrophotometry and mass spectrum (MSES) as follows:

Provenance & Evidence