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

HRID 1033420ノート

反応式

HRID 1033420 の反応式
[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]

参加物

7

反応物 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

生成物 1

HCID 186513982(R)-t-Butoxycarbonylamino-3-(t-butoxy)-N-[2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-3(R)-yl]propanamide収率 200%

試薬・触媒・溶媒 2

HCID 6344Dichloromethane溶媒HCID 8857Ethyl Acetate溶媒

実験手順

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 (200%) 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,205), 426 (M+Li,40%).

後処理

  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)

出典と根拠

ORDレコード
ord-0b6500a03afb46b6ba886646349e9b06
出典データセット
uspto-grants-1994_05
特許番号
US05310737

反応ノート

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