4-Toluenesulfonyl chloride → HCID 10945567, compound

Participants

Reaction Conditions

Reaction Steps

3.75 g of 2-chlorocrotononitrile are added to a solution of 5.16 g of para-toluenesulphonyl chloride in 120 cm3 of 1,2-dichloroethane. The solution obtained is clear. 4 g of the sodium salt of N-(2-chloronicotinoyl)piperidine-2-carboxylic acid are added with stirring. The addition causes a rise in temperature from 20° C. to 28° C. and the mixture is kept stirred for one hour at ambient temperature. 3.8 cm3 of triethylamine are then added dropwise and the temperature increases to 35° C. The solution is heated to 40° C. for one hour and 30 minutes. After cooling, the reaction mixture is concentrated at reduced pressure (2.7 kPa) at a temperature close to 60° C. A mixture of products is thus obtained which is chromatographed on a column of 1.8 cm diameter containing 90 g of silica (0.04-0.0063). Elution is carried out with chloroform at a pressure of 1.5 bar, 20-cm3 fractions being collected. The homogeneous fractions are combined and concentrated at reduced pressure (2.7 kPa) at a temperature close to 60° C. 2.81 g of 2-methyl-3-(2-chloro-3-pyridyl)-5,6,7,8-tetrahydroindolizine-1-carbonitrile are thus obtained in the form of cream crystals melting at about 134° C.

Provenance & Evidence