The title enantiomer was obtained by resolution of the racemic efaroxan (I) with (+)-dibenzoyl-D-tartaric acid to produce, after two recrystallizations from MeOH/Et2O, the desired pure diastereomeric salt, which was then liberated by treatment with K2CO3.

Alternatively, the title compound was prepared by an asymmetric synthesis: The known racemic 2-ethyl-2,3-dihydro-2-benzofurancarboxylic acid (II) was resolved by means of (S)-(+)-2-phenylglycinol to furnish the desired (+)-enantiomer (III). After esterification of (III) using MeOH in the presence of SOCl2, the resultant methyl ester (IV) was treated with ammonium hydroxide, yielding amide (V). Subsequent dehydration of amide (V) with P2O5 in refluxing toluene gave nitrile (VI). Treatment of (VI) with EtOH in the presence of a catalytic amount of NaOMe produced an intermediate imidate, which was subsequently treated with ethylenediamine and HCl to generate the title imidazoline.

Several alternative procedures have been further reported for the synthesis of the intermediate acid (II). The Darzens condensation of 2-fluorobenzaldehyde (VII) with ethyl 2-bromobutyrate (VIII) furnished epoxide (IX). Catalytic hydrogenation of epoxide (IX) gave rise to the hydroxy ester (X), which was hydrolyzed to acid (XI) under basic conditions. Cyclization of (XI) using NaH in hot DMF provided the racemic benzofurancarboxylic acid (II), which was then resolved with 2-phenylglycinol as above.

Preparation of the intermediate hydroxy ester (X) has been reported by a different method consisting in the addition of Grignard reagent (XIII), prepared from 2-fluorobenzyl bromide (XII), to ethyl 2-oxobutyrate.

Addition of the in situ-generated Grignard reagent from 2-fluorobromobenzene (XV) to the chiral epoxide (XVI) furnished hydroxy ester (XVII). This was cyclized to the benzofuran derivative (XVIII) by using NaH in hot DMF. Hydrogenolysis of the benzyl ether (XVIII) provided the primary alcohol (XIX), which was then oxidized to the target carboxylic acid (III) employing the Jones reagent in acetone.