تفاعل #70074

معادلة التفاعل

sodium hydrogen carbonate

hydrogen chloride methanol

methyl 2-(N-tert-butoxycarbonyl-N-{(2′-[1-(p-methoxybenzyl)-1H-tetrazol-5-yl]biphenyl-4-yl)methyl}amino)-3-nitrobenzoate

compound 20a

methyl 2-(N-tert-butoxycarbonyl-N-{(2′-[1-(p-methoxybenzyl)-1H-tetrazol-5-yl]biphenyl-4-yl)methyl}amino)-3-nitrobenzoate

→

methyl 2-[({2′-[1-(p-methoxybenzyl)-1H-tetrazol-5-yl]biphenyl-4-yl}methyl)amino]-3-nitrobenzoate

المردود 101.0%

المذيبات

toluene ethyl acetate

ظروف التفاعل

المعالجة

1. 1
   درجة الحرارةwarmed to 9° C. over 1 hr
2. 2
   درجة الحرارةThe reaction mixture was cooled to 3° C.
3. 3
   أخرىat 30° C.
4. 4
   استخلاصThe mixture was extracted twice with ethyl acetate (450 mL, 250 mL)
5. 5
   غسيلthe combined organic layers were washed with saturated brine (200 mL)
6. 6
   تجفيفdried over magnesium sulfate (10 g)
7. 7
   تركيزconcentrated under reduced pressure at 40° C.
8. 8
   workup.ADDITIONTo the concentrate was added chloroform
9. 9
   أخرىthe solvent was evaporated under reduced pressure in a bath at 40° C.

الإجراء التجريبي

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.

المصدر