Pseudoephedrine hydrolysis

This operation is necessary to hydrolyze the pseudoephedrine aminal which forms as a direct product of the reduction, in addition to the desired aldehyde. The use of the additional 700 mL of 1 N aqueous hydrochloric acid solution was found to be crucial for this hydrolysis reaction. 

To the solution of l-phenyl-l-methoxy-2-bromopropane methylamine was added and as a result of the reaction l-phenyl-l-methoxy-2-methylaminopropane was obtained. After that l-phenyl-l-methoxy-2-methylaminopropane on hydrolysis with hydrobromic acid yielded 1-phenyl-l-hydroxy-2-methylaminopropane, i.e. racemic pseudoephedrine. The racemic base was resolved, by crystallization of their tartrates, into I- and d-pseudoephedrine. The base l-pseudoephedrine forms white rhombic crystals, melting point 118°C. The salt pseudoephedrine sulfate may be prepeared by... 

Alkylation products of pseudoephedrine amides are readily transformed in a single operation into highly enantiomerically enriched carboxylic acids, aldehydes, ketones, lactones or primary alcohols. Alkylated pseudoephedrine amides can be hydrolyzed under acidic or basic conditions to form carboxylic acids. Simply heating a pseudoephedrine amide at reflux in a 1 1 mixture of sulfuric acid (9-18 N) and dioxane affords the corresponding carboxylic acid in excellent chemical yield with little or no epimerization (eq 7). Under these conditions, the substrate initially undergoes a rapid N— -0 acyl transfer reaction followed by rate-limiting hydrolysis of the resulting (3-ammonium ester intermediate to form the carboxylic acid. ... 

Basic conditions for the hydrolysis of pseudoephedrine amides typically involve heating the substrate with tetra-n-butylammo-nium hydroxide in a mixture of ferf-butyl alcohol and water... 

Hydrolysis reactions of alkylated pseudoephedrine glycina-mides are more rapid than the hydrolysis of pseudoephedrine amides without a-amino groups. It is believed that this reflects... 

Table 8 Basic hydrolysis of pseudoephedrine amides followed by iV-protection...

In the laboratory of T.F. Jamison, the synthesis of amphidinolide T1 was accomplished utilizing a catalytic and stereoselective macrocyclization as the key step. ° The Myers asymmetric alkylation was chosen to establish the correct stereochemistry at the C2 position. In the procedure, the alkyl halide was used as the limiting reagent and almost two equivalents of the lithium enolate of the A/-propionyl pseudoephedrine chiral auxiliary was used. The alkylated product was purified by column chromatography and then subjected to basic hydrolysis to remove the chiral auxiliary. 

The series on asymmetric synthesis then concludes with procedures for the preparation of enantiomerically pure products. The asymmetric syntheses of unnatural a-amino acids by the alkylation of pseudoephedrine glycin-amide is nicely exemplified by the preparation of l-ALLYLGLYCINE and N-BOC-i.-ALLYLGLYCINE. One of the advantages of this method is the ready availability of the chiral auxiliary and the mildness of the conditions required for the hydrolysis of the pseudophedrine amide to provide the a-amino acid. Biocatalytic transformations are also gaining importance in asymmetric synthesis as illustrated by the preparation of... 

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