反应详情

温度

60 °C

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%).

1. temperatureAfter the reaction mixture was cooled to room temperature
2. washThe organic layer was successively washed with water
3. dry with materiala saturated aqueous NaCl solution and dried with anhydrous sodium sulfate
4. customThe residue obtained
5. customby removing the solvent under reduced pressure
6. customwas purified by silica gel column chromatography (eluting solvent: n-hexane/ethyl acetate=4/1-1/3)