반응 #70074

ord-17df946ec69949f6b7f38cfc46566a8e

반응 조건

온도
3°CELSIUS
상세 조건
See reaction.notes.procedure_details.

후처리

  1. 1
    온도warmed to 9° C. over 1 hr
  2. 2
    온도The reaction mixture was cooled to 3° C.
  3. 3
    기타at 30° C.
  4. 4
    추출The mixture was extracted twice with ethyl acetate (450 mL, 250 mL)
  5. 5
    세척the combined organic layers were washed with saturated brine (200 mL)
  6. 6
    건조dried over magnesium sulfate (10 g)
  7. 7
    농축concentrated under reduced pressure at 40° C.
  8. 8
    workup.ADDITIONTo the concentrate was added chloroform
  9. 9
    기타the solvent was evaporated under reduced pressure in a bath at 40° C.

실험 절차

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.

출처

DOI: 10.6084/m9.figshare.5104873.v1특허: US08530506B2uspto-grants-2013_09