Acetic Anhydride → 5-Amino-5-oxopentanoic acid

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Reaction Steps

Accordingly, 3-isobutylglutaric acid, compound 1, is converted into the corresponding anhydride, compound 2, by treatment with acetic anhydride. The reaction of the anhydride with NH4OH produces the glutaric acid mono-amide, compound 3, which is resolved with (R)-1-phenylethylamine, yielding the (R)-phenylethylamine salt of (R)-3-(carbamoylmethyl)-5-methylhexanoic acid, compound 3-salt. Combining the salt with an acid liberates the R enantiomer, compound 4. Finally, Hoffmann degradation with Br2/NaOH provides (S)-Pregabalin.

Provenance & Evidence