(R)-1-(4-(2, 5-Dihydro-3-methyl-5-oxothien-2-ylidene)-4-(3-methyl-2-thienyl) butyl)-3- piperidinecarboxylic acid (5-hydroxytiagabine) 13, has been prepared in 8 steps from 2- bromo-3-methylthiophene 3. Key steps are Grignard reactions, displacement of heteroaromatic chlorine with methoxy, and simultaneously demethylation and opening of a hydroxymethylcyclopropane with bromotrimethylsilane. An alternative approach involving ...
