Experimental study demonstrates direct synthesis of Weinreb amides from carboxylic acids using titanium tetrachloride, highlighting a mild protocol that avoids column chromatography.
Reported herein is a mild, rapid, and operationally simple protocol for the direct synthesis of N ‐methoxy‐ N ‐methylamides (Weinreb amides) from carboxylic acids in the presence of TiCl 4 . The reaction proceeds under ambient conditions, overcoming the challenges encountered by existing amidation methodologies. The protocol accommodates a broad range of substrates, delivering both aliphatic and aromatic Weinreb amides in good to excellent yields. Notably, the simple workup procedure eliminates the need for column chromatography, further enhancing the practical appeal.
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Singh et al. (2026) studied this question.
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