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Transition-Metal-Free Esterification of Amides via Selective N-C Cleavage under Mild Conditions

Guangchen Li, Peng Lei, Michal Szostak*

*Department of Chemistry, Rutgers University, 73 Warren Street, Newark, New Jersey 07102, United States, Email:

G. Li, P. Lei, M. Szostak, Org. Lett., 2018, 20, 5622-5625.

DOI: 10.1021/acs.orglett.8b02323

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A general, transition-metal-free, and operationally simple method for esterification of amides proceeds under exceedingly mild conditions via a highly selective cleavage of N-C(O) bonds. The reaction offers broad substrate scope and excellent functional group tolerance.

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General Procedure for Esterification

An oven-dried vial equipped with a stir bar was charged with an amide substrate (neat, 1.0 equiv), alcohol (typically, 1.2 equiv) and K3PO4 (typically, 3.0 equiv), and placed under a positive pressure of nitrogen. THF (typically, 1.0 M) was added with vigorous stirring at room temperature, and the reaction mixture was stirred at room temperature for an indicated time. After the indicated time, the reaction mixture was diluted with CH2Cl2 (5 mL) and filtered. The organic layer was washed with water (1 x 5 mL), brine (1 x 5 mL), dried, and concentrated. A sample was analyzed by 1H NMR (CDCl3, 500 MHz) and GC-MS to obtain conversion, yield and selectivity using internal standard and comparison with authentic samples. Unless stated otherwise, the crude product was purified by flash chromatography (EtOAc/hexanes) to give analytically pure product.

Key Words


ID: J54-Y2018