合成路线1

Preparation of the title compound has been reported by two procedures. Catalytic hydrogenation of benzofuran-4-carboxylic acid (I) over Pd/C afforded the dihydrobenzofuran (II). Carboxyl group reduction in (II) with LiAlH4 and further Swern oxidation of the resulting alcohol (III) furnished aldehyde (IV). Knoevenagel condensation of aldehyde (IV) with dimethyl malonate provided the benzylidenemalonate (V), which was converted to the key cyclopropane derivative (VII) upon treatment with 2-nitropropane (VI) and potassium tert-butoxide. Hydrolysis and decarboxylation of the malonate ester (VII) was performed using NaCN in hot DMSO to yield acid (VIIIa-b) as a diastereomeric mixture. Recrystallization of (VIIIa-b) from acetonitrile-water allowed the separation of the major (+/-)-trans-isomer, which was then resolved by preparative chiral HPLC. The desired (R,R)-isomer (IX) was finally coupled with guanidine (X) via activation with CDI