反应详情

温度

3 °C

To hydrogen chloride-methanol (30%; 26.9 g, net 8.08 g, 222 mmol) was added methyl 2-(N-tert-butoxycarbonyl-N-{(2′-[1-(p-methoxybenzyl)-1H-tetrazol-5-yl]biphenyl-4-yl)methyl}amino)-3-nitrobenzoate (compound 20a, 5.00 g, 7.68 mmol) over 13 min by four portions at 4-5° C. The mixture was stirred at about 3° C. for 2 hr, and warmed to 9° C. over 1 hr. The reaction was monitored by TLC (eluent: toluene/ethyl acetate (2:1)). The reaction mixture was cooled to 3° C., and saturated aqueous sodium hydrogen carbonate solution (180 mL) was added dropwise thereto at 30° C. or lower. The mixture was extracted twice with ethyl acetate (450 mL, 250 mL), and the combined organic layers were washed with saturated brine (200 mL), dried over magnesium sulfate (10 g), and concentrated under reduced pressure at 40° C. or lower. To the concentrate was added chloroform, and the solvent was evaporated under reduced pressure in a bath at 40° C. to give methyl 2-[({2′-[1-(p-methoxybenzyl)-1H-tetrazol-5-yl]biphenyl-4-yl}methyl)amino]-3-nitrobenzoate (compound 21a, 4.27 g, 101%) as a yellowish brown amorphous solid.

1. temperaturewarmed to 9° C. over 1 hr
2. temperatureThe reaction mixture was cooled to 3° C.
3. customat 30° C.
4. extractionThe mixture was extracted twice with ethyl acetate (450 mL, 250 mL)
5. washthe combined organic layers were washed with saturated brine (200 mL)
6. dry with materialdried over magnesium sulfate (10 g)
7. concentrationconcentrated under reduced pressure at 40° C.
8. additionTo the concentrate was added chloroform
9. customthe solvent was evaporated under reduced pressure in a bath at 40° C.