Dimethyl Sulfoxide → Tert-butyl 2-hydroxy-6-[({4'-[2-hydroxy-1-(methoxycarbonyl)ethyl]-1,1'-biphenyl-4-yl}oxy)methyl]-3-(trifluoromethyl)benzoate

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Reaction Conditions

Reaction Steps

Dimethyl sulfoxide (3 ml), paraformaldehyde (90% purity, 300 mg) and sodium hydrogencarbonate (300 mg, 3.57 mmol) were added to tert-butyl 2-hydroxy-6-[({4′-[(methoxycarbonyl)methyl]-1,1′-biphenyl-4-yl}oxy)methyl]-3-(trifluoromethyl)benzoate (400 mg, 0.77 mmol) obtained in Example (6-9), and the mixture was stirred at 60° C. for 3 hours. After the reaction mixture was cooled to room temperature, it was diluted with ethyl acetate. The organic layer was successively washed with water and a saturated aqueous NaCl solution and dried with anhydrous sodium sulfate. The residue obtained by removing the solvent under reduced pressure was purified by silica gel column chromatography (eluting solvent: n-hexane/ethyl acetate=4/1-1/3) to give tert-butyl 2-hydroxy-6-[({4′-[2-hydroxy-1-(methoxycarbonyl)ethyl]-1,1′-biphenyl-4-yl}oxy)methyl]-3-(trifluoromethyl)benzoate as a colorless solid (246 mg, yield: 58%), tert-butyl 2-hydroxy-6-[({4′-[1-(methoxycarbonyl)vinyl]-1,1′-biphenyl-4-yl}oxy)methyl]-3-(trifluoromethyl)benzoate (37 mg, yield: 9%) and tert-butyl 2-hydroxy-6-[({4′-[2-hydroxy-1-hydroxymethyl-1-(methoxycarbonyl)ethyl]-1,1′-biphenyl-4-yl}oxy)methyl]-3-(trifluoromethyl)benzoate (112 mg, yield: 25%).

Provenance & Evidence