Palladium Catalyzed One-pot Synthesis Of Heteroaryl Tert- Butyl Esters

Derivatives of heteroaryl esters are one of the most important building blocks in drug discovery and are used as a source of carboxylic acid. An efficient protocol to synthesize aryl (heteroaryl) terf-butyl esters by using "one-pot" palladium-catalyzed cross-coupling reactions of 3-bromopyridine derivatives and bis(pinacolato)diboron has been successfully achieved.1. Synthesis of 3-bromopyridine deviativesAccording to the literature reports,21 3-bromopyridine derivatives were synthesized by using Suzuki coupling reaction, nucleophilic substitution and Buchwald-Hartwig amination reaction with 2,5-dibromopyridine,3,5-bromopyridine as starting materials. All products were characterized by GC-MS and 1HNMR.2. Optimization of the preparation of 3-pyridineboronic acid pinacol esterThe Cross-coupling reaction of 3-bromopyridine and bis(pinacolato)diboron was chosen as the model reaction to investigate the influence of revealed solvent, reaction temperature, the amount of KOAc and bis(pinacolato)diboron. The optimum conditions for the reaction are:Pd(OAc)2 as catalyst, PPh3 as ligand, Dioxane as solvents and KOAc as base.3. Palladium catalyzed one-pot synthesis of heteroaryl tert-butyl esters3-bromopyridines and bis(pinacolato)diboron were reacted under the optimum reaction conditions. After the end of Step 1, additional Pd(OAc)2 and PPh3 together with di(tert-butyl) carbonate were added to the reactions mixture to obtain the desired heteroaryl tert-butyl esters. In conclusion, a novel and efficient route to synthesis the heteroaryl esters have been developed. All products were characterized by GC-MS and 1H NMR,13C NMR and MS.