A Practical Pilot-Scale Synthesis of 4-Vinyl-2,3-dihydrobenzofuran Using Imidate Ester Chemistry and Phase-Transfer Catalysis

A two-step telescoped synthesis of 4-vinyl-2,3-dihydrobenzofuran ( 2 ) was demonstrated using imidate ester chemistry and phase-transfer catalysis. Treatment of 2,3-bis(2-hydroxyethyl)phenol ( 1 ) with the Vilsmeier reagent resulted in an in situ generation of a bis-imidate intermediate 4, which was converted to 4-(2-chloroethyl)-2,3-dihydrobenzofuran ( 6 ) via a sequential ring closure and chloride displacement reactions. Further dehydrohalogenation of 6 using a phase-transfer catalyst provided an excellent, cost-effective method to prepare high quality 4-vinyl-2,3-dihydrobenzofuran ( 2 ). The yields for the two-step telescoped process ranged from 83 to 90%.