Methanol → HCID 66721222, compound

Participants

Reaction Conditions

Reaction Steps

Add dropwise, in 1 h 30 min, 85.6 mL (85.6 mmol) of a 1N solution of boron tribromide in DCM to a solution of 19 g (42.8 mmol) of methyl 6-[3-(benzyloxy)-4-chlorophenyl]-5-(2-methylphenyl)pyridine-2-carboxylate in 70 mL of anhydrous DCM cooled under argon to −70° C., maintaining the temperature at −65° C. After stirring for 2 h at −70° C., add dropwise 20 mL (520 mmol) of anhydrous methanol, maintaining the temperature at −65° C. Bring the reaction mixture to RT, then concentrate under reduced pressure. Take up the residue in 100 mL of toluene and concentrate again. Repeat the operation two more times. Take up the residue obtained in 100 mL of methanol and cool under argon at 0° C., then add dropwise 9 mL (128 mmol) of thionyl chloride. Stir the reaction mixture for 48 h at RT, then concentrate under reduced pressure. Take up the residue obtained in 200 mL of EtOAc, cool to 0° C. and treat with 300 mL of a saturated aqueous solution of NaHCO3. After extraction, extract the aqueous phase again with 100 mL of EtOAc. Combine the organic phases, wash with 100 mL of water, dry over Na2SO4 and concentrate under reduced pressure. Purify the residue by silica gel column chromatography, eluting with a heptane/EtOAc gradient from 0 to 30% of EtOAc. After concentration under reduced pressure, we obtain 14.7 g of methyl 6-(4-chloro-3-hydroxyphenyl)-5-(2-methylphenyl)pyridine-2-carboxylate in the form of white powder.

Provenance & Evidence