Amination of aryl halides using copper catalysis 铜催化芳卤胺化反应.pdf

TETRAHEDRON LETTERS Pergamon Tetrahedron Letters 42 (2001) 3251–3254 Amination of aryl halides using copper catalysis Fengrui Lang,* Daniel Zewge, Ioannis N. Houpis and R. P. Volante Merck Research Laboratories, Department of Process Research, PO Box 2000, Rahway, NJ 07065, USA Received 16 February 2001; revised 12 March 2001; accepted 13 March 2001 Abstract—Bromopyridine 4 was converted into aminopyridine 5 under Cu O catalysis with an ethylene glycol solution of 2 ammonia in excellent yield (90%). The amination reaction features low (0.5 mol%) catalyst loading, mild reaction temperature (80°C) and low reaction pressure (50 psi). This protocol is further studied in the amination of a variety of aryl halides. © 2001 Elsevier Science Ltd. All rights reserved. Aryl amines in general, and aminopyridines in particular, prepared by amination of the bromopyridine 4 using are useful pharmacophores or intermediates1 in several benzophenone imine as a primary amine surrogate fol- classes of drug candidates. Traditionally, the most com- lowing the Buchwald/Hartwig protocol. However, a mon way to access these compounds is by amination of more direct amination strategy was desirable.5 Herein we the corresponding aryl halides using ammonia or ammo- report a direct, practical, and efficient conversion of 4 nium hydroxide as