Tetrahydrofuran → Methyl 4'-[(2-butyl-3H-thieno-(2,3-d)-imidazol-3-yl)-methyl]-(1,1'-biphenyl)-2-carboxylate

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Reaction Steps

360 mg of the product of step E of Examples 29 and 30 were dissolved at ambient temperature in 7 ml of tetrahydrofuran and 96 mg of sodium hydride at 50% in oil were added in two lots at ambient temperature. After hydrogen had been released, the mixture was stirred for 10 minutes under nitrogen. Then, 610 mg of methyl bromomethyl-(1,1'-biphenyl)-2-carboxylate (prepared according to EP 0,253,310) were added and the mixture was stirred at ambient temperature for 35 minutes. Then the solvent was evaporated off under nitrogen and 20 ml of water were added. Extraction was carried out with methylene chloride and the extracts were washed with water. The organic phase was dried, filtered and evaporated and the residue was chromatographed on silica (eluant: ethyl acetate 50 - cyclohexane 50) to obtain 600 mg of isomer A (Rf=0.40) and 250 mg of isomer B (Rf=0.28).

Provenance & Evidence