合成路线1

BRL 35135 may be obtained by the following synthetic procedures: Alkylation of 4-hydroxybenzaldehyde (I) with methyl chloroacetate in boiling acetone in the presence of potassium carbonate and a catalytic quantity of potassium iodide gives methyl 4-formylphenoxyacetate (II), which is condensed with nitroethane in glacial acetic acid in the presence of n-butylamine to give the nitrostyrene (III). Reduction of nitrostyrene (III) with steel wool and glacial acetic acid/methanol leads to methyl 4-(2-oxopropyl)phenoxyacetate (IV). Condensation of (IV) with alpha-(aminomethyl-3-chlorobenzenemethanol (VI) and hydrogenation of the resultant imine with platinum in methyl acetate leads to a mixture of diastereomers (VII). Pure BRL 35135 can be obtained from this mixture of diastereomers by fractional crystallization, and subsequent recrystallization, of the hydrobromide salt from methyl acetate-methanol. The ethanolamine (VI) is prepared by addition of trimethylsilyl cyanide to 3-chlorobenzaldehyde (V) in diethyl ether in the presence of a catalytic amount of zinc iodide and subsequent reduction of the trimethylsilylcyanohydrin with lithium aluminum hydride.