The conformation at the amide functional group in 3,5‐dimethylisoxazole‐4‐(S‐2′‐hydroxymethyl‐N‐pyrrolidino) carboxamide 1 has been determined by a single crystal X‐ray determination. The 13C nmr in both deuteriochloroform solution and solid state show close agreement. The metalation behaviour of the amide is dependent upon the substitution on the 2′‐hydroxymethyl moiety. Dianion studies indicate C‐5 lateral metalation under both thermodynamic and kinetic conditions. Protection of this substituent as the methyl ether, 2, gives rise to predominant C‐3 lateral metalation under kinetic conditions and C‐5 lateral metalation on equilibration. These observations can be explained using the Ireland‐Evans model for chelation directed deprotonation.