Triethylamine → 2(R)-t-Butoxycarbonylamino-3-(t-butoxy)-N-[2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-3(R)-yl]propanamide

HRID 1591476Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1591476
[NH2:1][C@@H:2]1[CH2:8][CH2:7][C:6]2[CH:9]=[CH:10][CH:11]=[CH:12][C:5]=2[NH:4][C:3]1=[O:13].C(N(CC)CC)C.[C:21]([O:25][CH2:26][C@H:27]([C:36](O)=[O:37])[NH:28][C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])([CH3:24])([CH3:23])[CH3:22].F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1>C(Cl)Cl.C(OCC)(=O)C>[C:32]([O:31][C:29]([NH:28][C@H:27]([CH2:26][O:25][C:21]([CH3:24])([CH3:23])[CH3:22])[C:36]([NH:1][C@@H:2]1[CH2:8][CH2:7][C:6]2[CH:9]=[CH:10][CH:11]=[CH:12][C:5]=2[NH:4][C:3]1=[O:13])=[O:37])=[O:30])([CH3:35])([CH3:34])[CH3:33]

Komponenten

7

Edukt 4

HCID 8471TriethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 6992546(R)-3-(tert-Butoxy)-2-((tert-butoxycarbonyl)amino)propanoic acidHCID 10103689(R)-3-amino-4,5-dihydro-1H-benzo[b]azepin-2(3H)-one

Produkt 1

HCID 186513982(R)-t-Butoxycarbonylamino-3-(t-butoxy)-N-[2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-3(R)-yl]propanamideAusbeute 101,3 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6344DichloromethaneLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

To a solution of 200 mg (1.13 mmol) of 3(R)-amino-2,3,4,5-tetrahydro-1H-1-benzazepin-2-one (Example 1, Step B) in 8 mL of dry methylene chloride was added 0.206 mL (1.48 mmol) of triethylamine, 553 mg (1.25 mmol) of BOC-D-serine t-butyl ether followed by 602 mg (1.36 mmol) of benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate. The reaction mixture was stirred at room temperature for 2 hours then diluted with 100 mL of ethyl acetate, washed with 25 mL of 5% aqueous citric acid, 25 mL of saturated sodium bicarbonate and 25 mL of brine. The organic layer was dried over magnesium sulfate, filtered and the solvents removed under vacuum. The residue was purified by flash chromatography on silica gel, eluting with ethyl acetate/hexane (55:45) to afford 480 mg (100%) of the product as a white foam. 1H NMR (200 MHz,CDCl3): 1.20 (s,9H), 1.47 (s,9H), 1.92 (m,1H), 2.55-3.02 (m,3H), 3.38 (t,8 Hz,1H), 3.78 (m,1H), 4.15 (m,1H), 4.52 (m,1H), 5.45 (s,1H), 7.00 (m,1H), 7.10-7.35 (m,3H), 7.68 (d,4 Hz,1H), 8.05 (s,1H). FAB-MS: calculated for C22H33N3O5 419; found 420 (M+H,20%), 426 (M+Li,40%).

Aufarbeitung

  1. washwashed with 25 mL of 5% aqueous citric acid, 25 mL of saturated sodium bicarbonate and 25 mL of brine
  2. dry with materialThe organic layer was dried over magnesium sulfate
  3. filtrationfiltered
  4. customthe solvents removed under vacuum
  5. customThe residue was purified by flash chromatography on silica gel
  6. washeluting with ethyl acetate/hexane (55:45)

Quellen und Nachweise

ORD-Eintrag
ord-51d9bfb254af4d869f083023a8141e4f
Quelldatensatz
uspto-grants-1993_04
Patentnummer
US05206235

Notizen zur Reaktion

Wird geladen…