A short and efficient synthesis of 4-aminomethyl-4-fluoropiperidines and 3-aminomethyl-3-fluoropyrrolidines is described. These fluorinated azaheterocycles are of specific interest as bifunctional building blocks for fluorinated pharmaceutical compounds. The key step of the synthetic pathway involves the regioselective bromofluorination of N-Boc-4-methylenepiperidine and 3-methylenepyrrolidine using Et(3)N.3HF and NBS.
A synthetic route towards 1-t-butoxycarbonyl-3-fluoro-3-methylpyrrolidine and 1-tbutoxycarbonyl-3-fluoro-3-methylazetidine, which are interesting building blocks for pharmaceutical compounds, is described. The key steps include a bromofluorination of appropriate alkenyl azides, followed by reduction to the corresponding amines and subsequent cyclization, yielding the 3-fluorinated azaheterocycles.
A copper‐mediated cross‐coupling of difluoroacetate (II) with haloarenes followed by hydrolysis of the nitrile group/cyclization gives access to title compounds.
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