Water → 1-Benzofuran-3-carboxylic acid

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Reaction Steps

To a solution of benzofuran (75 g) in chloroform (600 ml) was added dropwise a solution of bromine (41 ml) in chloroform (150 ml) at -10° C. The temperature was slowly allowed to reach room temperature and chloroform was evaporated in vacuo, leaving the crude 2,3-dibromo-2,3-dihydrobenzofuran as a crystalline product which was used without further purification. Yield: 171 g. To the dibromoderivative (147 g) in ethanol (600 ml) was added a solution of KOH (59 g) in ethanol (200 ml). The mixture was refluxed for 2.5 hours. After cooling to room temperature the mixture was poured onto water and extracted with ethyl acetate (2×300 ml). The combined organic phases were worked-up and the 3-bromobenzofuran was subsequently purified by elution through silica gel using n-heptane as the eluent. Yield 51 g of a semicrystalline product. A solution of all of the thus obtained 3-bromobenzofuran and CuCN (33 g) in N-methyl-2-pyrrolidinone (350 ml) was heated at 190° C. under N2. With 1 hour intervals was added further CuCN (3×4.5 g). The mixture was poured into a solution of FeCl3.6H2O in water (610 ml) and concentrated hydrochloric acid (156 ml) while still hot. The resulting mixture was stirred at 60° C. for 1 hour and subsequently poured onto ice/water (5 l). Extraction with diethyl ether (3×300 ml) and working-up of the combined organic phases afforded crude, crystalline 3-cyanobenzofuran melting at 76°-82° C. Yield : 34 g. The 3-cyanobenzofuran was dissolved in a mixture of acetic acid:conc. H2SO4 :water 1:1:1 (660 ml) and refluxed for 3 hours. After cooling water was added and the 3-benzofurancarboxylic acid was finally extracted with diethyl ether (3×200 ml) and worked-up. Yield 37 g. Mp: 152°-156° C.

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