1,2,3,6-Tetrahydro-1-methyl-4-(2,4,6-trimethoxyphenyl)-3-pyridinol → (3S,4R)-1-Methyl-4-(2,4,6-trimethoxyphenyl)-3-piperidinol

Participants

Reaction Steps

Disclosed is a method for producing (−)cis-3-hydroxy-1-methyl-4-(2,4,6-trimethoxyphenyl)-piperidine characterized in that 1-methyl-piperidine-4-one is converted into hydrobromide, subsequently transformed with bromine into 3(R,S)-bromine-1-methyl-4-oxo-piperidine-hydrobromide and reacted with 1,3,5-trimethoxybenzol to form 3(R,S)-bromine-1-methyl-4-(2,4,6-trimethoxyphenyl)-1,2,3,6-tetrahydro-pyridine-hydrobromide. By stirring the reaction solution into an organic solvent, 3(R,S)-bromine-1-methyl-4-(2,4,6-trimethoxyphenyl)-1,2,3,6-tetrahydro-pyridine-hydrobromide is initially isolated as a solid and subsequently the product is mixed with water and converted into 3(R,S)-hydroxy-1-methyl-4-(2,4,6-trimethoxyphenyl)-1,2,3,6-tetrahydro-pyridine by means of stirring. The product thus prepared is catalytically hydrogenated into a racemic 3,4-cis-alcohol and subsequently, enantiomerically pure (−)cis-3-hydroxy-1-methyl-4-(2,4,6-trimethoxyphenyl)-piperidine is obtained by separation of racemic mixtures with chiral auxiliary reagents from racemic 3,4-cis alcohol.

Provenance & Evidence