It can be prepared in three different ways): 1) By reduction of 2-ethylbenzofuran (I) with H2 over Pd/C in acetic acid yields 2-ethyl-2,3-dihydrobenzofuran (II). The Friedel-Crafts acetylation of (II) with acetic anhydride and AlCl3 in methylene chloride gives 2-ethyl-5-acetyl-2,3-dihydrobenzofuran (III), which is treated with sulfur in refluxing morpholine (IV) to yield 2-ethyl-2,3-dihydrobenzofuran-5-acetothiomorpholide (V). Hydrolysis of (V) with NaOH affords furofenac.
2) By reduction of 2-ethylbenzofuran (I) with H2 over Pd/C in acetic acid yields 2-ethyl-2,3-dihydrobenzofuran (II). The Friedel-Crafts acylation of (II) with ethyl chlorooxalate (VI) gives 2-ethyl-2,3-dihydrobenzofuran-5-oxalic acid ethylester (VII). Hydrolysis of this compound with NaOH followed by reduction with hydrazine hydrate and KOH in diethyleneglycol yields furofenac.
3) By reduction of 2-ethylbenzofuran (I) with H2 over Pd/C in acetic acid yields 2-ethyl-2,3-dihydrobenzofuran (II). The chloromethylation of (II) gives 2-ethyl-5-chloromethyl-2,3-dihydrobenzofuran (IX), which is converted into 2-ethyl-2,3-dihydrobenzofuran-6-acetonitrile (X) by reaction with KCN in refluxing ethanol. Hydrolysis of (IX) with concentrated HCl yields furofenac.