2-Dimethylaminopyridine → HCID 10077331, compound

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Reaction Steps

Dissolve the product of Example 3 (220 mg, 0.43 mmol) in pyridine (5 mL) and treat sequentially with trimethylacetyl chloride (0.144 mL, 1.17 mmol) and dimethylaminopyridine (DMAP, catalytic amount). Stir at ambient temperature for 18 hours and evaporate pyridine. Re-constitute the residue in ethyl acetate and wash with saturated aqueous NH4Cl, saturated aqueous NaHCO3, and brine. Dry the organic layer (Na2SO4), filter, and evaporate to obtain 277 mg of crude material. Pre-adsorb onto silica gel and chromatograph on a SiO2 column eluting the material with methanol in dichloromethane (0 to 6%) to give 235 mg of 2,2-dimethyl-propionic acid 6-(4-methanesulfonyl-phenyl)-5-[4-(2-piperidin-1-yl-ethoxy)-phenoxy]-naphthalen-2-yl ester. Dissolve the free base in a mixture of ethyl acetate and diethyl ether (20 mL; 1:1). Cool in an ice bath and treat with 2M HCl in diethyl ether (0.3 mL, 0.6 mmol). Collect the precipitate on filter paper and rinse with diethyl ether to obtain 220 mg of the title compound (80%): mass spectrum (ion spray): m/z=602.4 (M+H—HCl).

Provenance & Evidence