Preparation of gabapentin analogues comprised of adding cyclohexanone to sodium hydride and finally heating the formed lactam in HCl and dioxan

摘要

A process for preparing a compound of the Formula (I) comprising: a) adding cyclohexanone to a mixture of sodium hydride suspended in dry tetrahydrofuran to which triethyl phosphonoacetate was added; b) partitioning the mixture between HCl and diethyl ether and collecting the ether layer; c) dissolving the product of step (b) the a,b-unsaturated ester in THF with nitromethane and tetrabutylammonium fluoride and heating the resulting mixture to produce a nitro ester; d) dissolving the product of step (c) a nitro ester in methanol and shaking in the presence of H2 over a catalyst to produce the corresponding lactam; and e) heating the product of step (d) a lactam, to reflux in a mixture of HCl and dioxan to produce a compound of the Formula (I), and converting, if desired, to a pharmaceutically acceptable salt.