By condensation of 2-hydroxy-2-phenylethylamine (I) with 1-(4-methoxycarbonylphenyl)-2-propanone (II) in refluxing benzene, followed by reduction with NaBH4 in methanol, and treatment with maleic acid (III).
The synthesis of [14C]-labeled BRL-26830A has been described: The reaction of copper sulfate (I) with sodium methabisulfite, followed by treatment with [14C]-labeled potassium cyanide (II) yields cuprous cyanide (III), which is condensed with methyl 4-bromobenzoate (IV) to afford methyl 4-cyanobenzoate (V). The reduction of (V) with Al/Ni and formic acid gives methyl 4-formylbenzoate (VI), which is condensed with nitroethane by means of butylamine and acetic acid in benzene to give methyl 4-(2-nitro-1-propenyl)benzoate (VII). The treatment of (VII) with Fe and HCl in refluxing methanol yields methyl 4-(acetonyl)benzoate (VIII), which is reductocondensed with (R*)-2-amino-1-phenylethanol (IX) by means of NaBH4 in refluxing benzene and crystallized in methanol to fractionate the optical diastereomers. Finally, the (R*,R*)-isomer (X) is treated with fumaric acid.