Triethylamine → 2,4-Dinitrobenzoyl chloride

Participants

Reaction Steps

As shown in scheme B, treatment of 2,4-dinitrobenzoic acid with chlorinating agent such as thionyl chloride gave 2,4-dinitrobenzoyl chloride which on further treatment with benzyl glycinate in the presence of triethylamine gave benzyl 2-(2,4-dinitrobenzamido)acetate (intermediate 1). The intermediate 1 is treated either with K18F or K19F in the presence of a catalyst such as kryptofix[2.2.2] or 18-crown-6 to yield benzyl 2-(2-fluoro-4-nitrobenzamido)acetate, which on reduction with hydrogen gas or hydrogen source in the presence of Pd/C gave 2-(4-amino-2-fluorobenzamido)acetic acid (compound 1) in good yield. Alternatively, treatment of 2,4-dinitrobenzoyl chloride with glycine in presence of a mild base such as sodium carbonate gave 2-(2,4-dinitrobenzamido)acetic acid (intermediate 2). Treatment of intermediate 2 either with K18F or K19F gave 2-(2-fluoro-4-nitrobenzamido)acetic acid, which on reduction with zinc dust and ammonium formate or hydrogen gas/hydrogen source in the presence of Pd/C gave compound 1. Treatment of intermediate 2 either with K18F or K19F and further reduction with iron powder in the presence of acetic anhydride-acetic acid gave 2-(4-acetamido-2-fluorobenzamido)acetic acid (compound 2).

Provenance & Evidence