Tetrahydrofuran → 1-[3-(1-Methyl-1H-imidazol-2-ylmethoxymethyl)-phenyl]-1H-imidazole-4-carboxylic acid ethyl ester

Participants

Reaction Steps

To a suspension of NaH (308 mg, 7.7 mmol, 60% in mineral oil) in dry THF (6 mL) under N2 atmosphere was added a solution of alcohol 7 (410 mg, 1.38 mmol) in THF (2 mL) while stirring for 30 min at room temperature. The reaction mixture was cooled to 0° C. and the compound 14 (crude 200 mg, 1.53 mmol) in THF (1 mL) was added dropwise and allowed to come to room temperature during a period of 30 min after which it was refluxed for 12 h. The mixture was quenched with ice water (5 mL), acidified to pH 2-3 by adding aqueous HCl solution (2N). The reaction mixture was extracted with CH2Cl2 (3×20 mL), washed with brine, dried over Na2SO4 and concentrated. The crude mass was taken in ethanol (10 mL), purged HCl gas for 30 min. and stirred at room temperature for 3 h. After evaporation of solvent, the crude mass was purified by column chromatography using 28% ethylacetate in hexane to furnish 14a (150 mg, 25%) as a white solid, mp-83.8-88.6° C.

Provenance & Evidence