2-Benzofurancarboxylic acid, 5,6-dimethoxy- synthesis

Yield:114842-08-9 99%

Reaction Conditions:

Stage #1: 3-bromo-6,7-dimethoxy-2H-chromen-2-onewith sodium hydroxide in ethanol at 79; for 0.0833333 h;Microwave irradiation;Perkin rearrangement;
Stage #2: with hydrogenchloride in water; pH=1;

Steps:

5,6-Dimethoxy-3-methyl-benzofuran-2-carboxylic acid (2a)

General procedure: 3-Bromo-4-methyl-6,7-dimethoxycoumarin (1a) (0.05 g, 0.167 mmol) was added to a microwave vessel. Ethanol (5 ml) and sodium hydroxide (0.0201 g, 0.503 mmol) were then added to the vessel that was then sealed and inserted into the microwave for 5 min, at 300 W and at a temperature of 79 °C with stirring. The reaction was monitored by thin layer chromatography (silica gel, 3:1 CH₂Cl₂/EtOAc). Upon completion of the reaction, the mixture was concentrated on a rotary evaporator and the resultant crude product obtained was dissolved in the minimum volume of water. This solution was acidified with concentrated hydrochloric acid to pH 1 resulting in precipitation of an off-white solid which was collected by vacuum filtration and dried in an oven at 80 °C to yield 3-methyl-5,6-dimethoxybenzofuran-2-carboxylic acid (2a, 0.039 g, 99%),

References:

Marriott, Karla-Sue C.;Bartee, Rena;Morrison, Andrew Z.;Stewart, Leonard;Wesby, Julian [Tetrahedron Letters,2012,vol. 53,# 26,p. 3319 - 3321] Location in patent:experimental part