反応 #1832

ord-48cc48b39ac845098b60f3e2837e0e56

反応条件

詳細条件
See reaction.notes.procedure_details.

後処理

  1. 1
    その他was immersed in an ambient temperature
  2. 2
    洗浄washed three times with 5% aqueous citric acid
  3. 3
    その他The organic layer was removed
  4. 4
    乾燥dried over magnesium sulfate
  5. 5
    ろ過filtered
  6. 6
    濃縮the filtrate concentrated under vacuum
  7. 7
    その他The residue was purified by preparative high pressure liquid chromatography on silica
  8. 8
    洗浄eluting with ethyl acetate/hexane (4:1)

実験手順

A solution of 8.70 g (49.4 mmol) of 3(R)-amino-2,3,4,5-tetrahydro-1H-1-benzazepin-2-one (Step E) in 100 mL of methylene chloride was treated with 10.73 g (49.4 mmol) of 3-t-butoxycarbonylamino-3-methylbutanoic acid (Step H) and 13.8 mL of triethylamine (10.0 g, 99 mmol, 2 eq.). The reaction flask was immersed in an ambient temperature water bath then 26 g of benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (59 mmol, 1.2 eq) was added all at once and the mixture stirred at room temperature for 2 hours. The reaction mixture was added to 300 mL of ethyl acetate and washed three times with 5% aqueous citric acid, twice with saturated aqueous sodium bicarbonate and once with saturated aqueous sodium chloride. The organic layer was removed, dried over magnesium sulfate, filtered and the filtrate concentrated under vacuum. The residue was purified by preparative high pressure liquid chromatography on silica, eluting with ethyl acetate/hexane (4:1), to afford 17.42 g (46.4 mmol, 94%) of the product as a white solid. 1H NMR (200 MHz,CDCl3): 1.37 (s,6H), 1.44 (s,9H), 1.95 (m,1H), 2.46 (d,15 Hz,1H), 2.59 (d,15 Hz,1H), 2.6-3.0, (m,3H), 4.53 (m,1H), 5.30 (br s,1H), 6.72 (d,7 Hz,1H), 6.98 (d,8 Hz,1H), 7.1-7.3 (m,3H), 7.82 (br s,1H). FAB-MS: calculated for C20H29N3O4 375; found 376 (M+H,70%).

出典

DOI: 10.6084/m9.figshare.5104873.v1特許: US05726307uspto-grants-1998_03