Tetrabutylammonium Fluoride → 3-[(1R)-1-(2-chlorophenyl)-2-hydroxyethoxy]-5-[6-(hydroxymethyl)-1H-imidazo[4,5-c]pyridin-1-yl]thiophene-2-carboxamide

Participants

Reaction Conditions

Reaction Steps

A mixture of 236 mg of 3-[(1R)-2-{[tert-butyl(dimethyl)silyl]oxy}-1-(2-chlorophenyl)ethoxy]-5-[6-({[tert-butyl(dimethyl)silyl]oxy}methyl)-1H-imidazo[4,5-c]pyridin-1-yl]thiophene-2-carboxamide in 15 ml THF is cooled to 0° C. At 0° C. 0.26 ml tetra-n-butylammonium fluoride (˜75% in H20) are added. The reaction mixture is allowed to warm to room temperature and stirred for one hour. The solvent is evaporated under reduced pressure and the residue is treated with 15 ml dichloromethane and 10 ml saturated aqueous NaHCO3 solution. The phases are separated; the aqueous phase is extracted with 10 ml dichloromethane. The combined organic phase is dried over Na2SO4, filtered and concentrated to dryness. The raw product is purified by flash chromatography over silica gel Flash NH2 [eluent: dichloromethane/methanol, with a gradient of 100/0 to 90/10 (v/v)]. The title product is obtained after a second purification in preparative HPLC (ammonium formate buffer/acetonitrile, elution gradient 80/20 to 30/70 (v/v)).

Provenance & Evidence