N,N-Dimethyl-4-(4-methylphenyl)-4-oxobutyramide (I) with Br2 in HOAc gives the 3-bromo derivative (II), which is cyclized with 5-methylpyridine-2-amine (III) in either hot acetonitrile or 1,3-dimethyl-2-imidazolidinone to afford the imidazo-pyridine derivative (IV). Finally, the semitartrate salt is obtained by treatment of (IV) with tartaric acid in MeOH. Alternatively, the conversion of N,N-Dimethyl-4-(4-methylphenyl)-4-oxobutyramide (I) into the imidazo-pyridine derivative (IV) can be directly performed by first refluxing of (I) with HBr in dichloromethane, followed by reaction with Br2 and final treatment with a solution of 5-methylpyridine-2-amine (III) in acetonitrile.

A new and industrially viable synthesis of zolpidem has been described: The cyclization of 2-amino-5-methylpyridine (I) with 4-methylphenacyl bromide (II) gives 6-methyl-2-(4-methylphenyl)imidazo[1,2-a]pyridine (III), which is condensed with N,N-dimethylglyoxylamide (IV) to yield 2-hydroxy-N,N-dimethyl-2-[6-methyl-2-(4-methylphenyl)imidazo[1,2-a]pyri din-3-yl]acetamide (V). The reaction of (V) with SOCl2 affords the corresponding chloroacetamide (VI), which is finally reduced to give zolpidem. This product is then converted into the hemitartrate salt. Via this synthesis, zolpidem is obtained in excellent yield and quality on an industrial scale.