Synthesis of 6-fluoro-3,4-dihydro-2H-1-benzopyran-2-carboxylic Acid

6-Fluro-3,4-dihydro-2H-1-benzopyran-2-carboxylic acid is the key intermediate of Nebivolol, a new antihypertensive agent. The process for the synthesis of its racemics was studied, which involves 6 steps including esterification, rearrangment, acylation, cyclization, hydrolyzation and hydrogenation with an overall yield of 27%. 4-Fluorophenol (I) is firstly esterified with acetic anhydride to give 4-fluorophenyl acetate (II), which is rearranged in the presence of anhydrous AlCl3 to afford 4-fluoro-2-acetyl phenol (III) with a higher yield(58%) than that obtained by direct acylation of 4-fluorophenol. III is transformed into 6-fluoro-4-oxo-4H-1-benzopyran-2-car -boxylic acid (VI) by treatment with diethyloxalate via acylation,cyclization and hydrolyzation, that is to say, the above three reactions finished by using a single agent. The title product, 6-fluoro-3,4-dihydro-2H-1-benzopyran-2-carboxylic acid(VII) was finally obtained from the reduction of VI by hydrogen with 10% Pd/C as catalyst in acetic acid. The process proposed has the potential perspective to be industrialized due to the mild conditions and readily available agents. The spectra of IR and 1H-NMR of the title compound and its key intermediate were reported to identify the structure of the product.