(3-Bromopropyl)benzene → (1R,3R)-3-(2-Hydroxy-2,2-di-thiophen-2-yl-acetoxy)-1-methyl-1-(3-phenyl-propyl)-piperidinium bromide

Participants

Reaction Conditions

Reaction Steps

Hydroxy-di-thiophen-2-yl-acetic acid (R)-1-methyl-piperidin-3-yl ester (2.1 g, 0.00623 mol) is dissolved in acetonitrile (5 ml) at 60° C. and 1-bromo-3-phenylpropane (1.43 ml, 0.00934 mol) is added dropwise. After 18 hours stirring at 60° C., the white solid is broken up and stirring continued for another 8 hours at this temperature. The suspension is cooled to room temperature and the solid filtered off. The solid is recrystallised from 3 ml of acetonitrile containing 2 drops of water to yield (1R,3R)-3-(2-Hydroxy-2,2-di-thiophen-2-yl-acetoxy)-1-methyl-1-(3-phenyl-propyl)-piperidinium bromide (96a) as a white solid. The reaction mixture mother liquid is evaporated to dryness and the residue is purified by flash chromatography over C18 silica gel (70 g) using a gradient of water/acetonitrile 10010 to 0/100 over 25 minutes at 20 ml/min. The product containing fractions are combined and evaporated to dryness to yield (1S,3R)-3-(2-hydroxy-2,2-di-thiophen-2-yl-acetoxy)-1-methyl-1-(3-phenyl-propyl)-piperidinium bromide (96b) as a white amorphous solid.

Provenance & Evidence