合成路线1

1) Reductive amination of phenylacetone (I) with ammonium acetate and sodium cyanoborohydride (I) gives d,l-amphetamine (II), which is separated by distillation at reduced pressure from a secondary amine byproduct resulting from reaction of amphetamine with phenylacetone. Iodination of the N-acetyl-protected amine followed by acid hydrolysis yields a mixture of ortho-meta and para substituted iodoamphetamine, from which the para-isomer can be obtained by crystallization of the salt (IV) from hydrochloric acid. Reductive condensation of the primary amine salt with acetone and sodium cyanoborohydride then yields ofetamine (V). The free base is converted to the hydrochloride salt (VI) by treatment with dry HCl gas in ether. The acetate salt may be prepared by treatment of the free base with glacial acetic acid in ether, followed by addition of hexane or petroleum ether to precipitate the product.