Pentafluoropyridine → Imidazole

Participants

Reaction Conditions

Reaction Steps

1.6 M nBuLi (66 ml; 45 mmol) is added at −45° C. to a ˜1:1 mixture of 1-(1,1-diethoxymethyl)-4-(4-fluorophenyl)-5-(4-pyridinyl)imidazole and 1-(1,1-diethoxymethyl)-5-(4-fluorophenyl)-4-(4-pyridinyl)imidazole (15 g; 43 mmol) in THF (210 ml). After 15 min. at −45° C. the reaction mixture is cooled to −55° C. and pentafluoropyridine (5.1 ml; 47 mmol) is rapidly introduced. The cooling bath is removed, the reaction mixture allowed to warm to −15° C. and poured on water (1 l), which is then acidified with 2N HCl (100 ml). After stirring for 5 min. the mixture is combined with a saturated solution of Na2CO3 and extracted with ethyl acetate three times. The combined organic phases are dried over Na2SO4, filtered and evaporated to dryness rendering the title compound as brownish crystals (16.3 g). Chromatography (SiO2; acetone/hexanes 1:1) yields the title compound together with some unreacted and unprotected imidazole starting material, which could be removed by washing with acetone yielding the title compound (8.7 g; 52.4%).

Provenance & Evidence