Реакция #1832

ord-48cc48b39ac845098b60f3e2837e0e56

Уравнение реакции

CN(C)[P+](On1nnc2ccccc21)(N(C)C)N(C)C.F[P-](F)(F)(F)(F)F
benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate
N[C@@H]1CCc2ccccc2NC1=O
3(R)-amino-2,3,4,5-tetrahydro-1H-1-benzazepin-2-one
CC(C)(CC(=O)O)NC(=O)OC(C)(C)C
3-t-butoxycarbonylamino-3-methylbutanoic acid
CCN(CC)CC
triethylamine
CC(C)(CC(=O)N[C@@H]1CCc2ccccc2NC1=O)NC(=O)OC(C)(C)C
product
Выход 94.0%
CC(C)(CC(=O)N[C@@H]1CCc2ccccc2NC1=O)NC(=O)OC(C)(C)C
3-t-Butoxycarbonylamino-3-methyl-N-[2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-3(R)-yl]-butanamide
Выход 94.0%

Растворители

Условия реакции

Подробные условия
See reaction.notes.procedure_details.

Обработка

  1. 1
    Другоеwas immersed in an ambient temperature
  2. 2
    Промывкаwashed three times with 5% aqueous citric acid
  3. 3
    ДругоеThe organic layer was removed
  4. 4
    Сушкаdried over magnesium sulfate
  5. 5
    Фильтрацияfiltered
  6. 6
    Концентрированиеthe filtrate concentrated under vacuum
  7. 7
    ДругоеThe residue was purified by preparative high pressure liquid chromatography on silica
  8. 8
    Промывкаeluting with ethyl acetate/hexane (4:1)

Методика

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%).

Источник

DOI: 10.6084/m9.figshare.5104873.v1Патент: US05726307uspto-grants-1998_03