By condensation of 3-chloro-5-(3-methylsulfonyloxypropyl)-10,11-dihydro-5H-dibenzo[b,f]azepine (I) with 1,2,3,5,6,7,8,8a-octahydroimidazo[1,2-a]pyridine-3-spiro 4'-piperidin-2-one (II) by means of K2CO3 in hot ethanol, and treatment with HCl.
The synthesis of the optical isomers of mosapramine has been reported: A solution of racemic spiro(octahydroimidazo[1,2-a]pyridine-3,4'-piperidin)-2-one (I) with N-acetyl-L-tryptophan in hot isopropanol is allowed to crystallize. The precipitate collected is recrystallized from isopropanol and treated with aqueous NH4OH, extracted with CHCl3, evaporated and crystallized from isopropanol to obtain the R-(-)-enantiomer of (I). The condensation of R-(-)-(I) with 3-chloro-5-[3-(methanesulfonyloxy)propyl]-10,11-dihydro-5H-dibenzo[b,f] azepine (II) by means of triethylamine in refluxing CHCl3 affords the R-(-)-isomer of mosapramine. The mother liquors of the separation of R-(-)-(I) are treated with aqueous NH4OH and extracted with CHCl3. This extract is purified by treatment with N-acetyl-D-tryptophan to obtain S-(+)-(I), which is then condensed with (II) as before, yielding the S-(+)-isomer of mosapramine.