2-Ethoxy-1-(ethoxycarbonyl)-1,2-dihydroquinoline → 3-t-Butoxycarbonylamino-3-methyl-N-benzyl-N-[2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-3-(R)-yl]-butanamide

HRID 1033406Notes

Reaction equation

HRID 1033406 reaction equation
[CH2:1]([NH:8][C@@H:9]1[CH2:15][CH2:14][C:13]2[CH:16]=[CH:17][CH:18]=[CH:19][C:12]=2[NH:11][C:10]1=[O:20])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:21]([O:25][C:26]([NH:28][C:29]([CH3:35])([CH3:34])[CH2:30][C:31](O)=[O:32])=[O:27])([CH3:24])([CH3:23])[CH3:22].C(OC1C=CC2C(=CC=CC=2)N1C(OCC)=O)C>O1CCCC1>[C:21]([O:25][C:26]([NH:28][C:29]([CH3:35])([CH3:34])[CH2:30][C:31]([N:8]([CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)[C@@H:9]1[CH2:15][CH2:14][C:13]2[CH:16]=[CH:17][CH:18]=[CH:19][C:12]=2[NH:11][C:10]1=[O:20])=[O:32])=[O:27])([CH3:24])([CH3:23])[CH3:22]

Participants

5

Reactant 3

HCID 278332-Ethoxy-1-(ethoxycarbonyl)-1,2-dihydroquinolineHCID 103760463-((tert-Butoxycarbonyl)amino)-3-methylbutanoic acidHCID 544972723(R)-(benzylamino)-2,3,4,5-tetrahydro-1H-benzazepin-2-one

Product 1

HCID 186514863-t-Butoxycarbonylamino-3-methyl-N-benzyl-N-[2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-3-(R)-yl]-butanamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 90 mg (0.34 mmol) of 3(R)-(benzylamino)-2,3,4,5-tetrahydro-1H-1-benzazepin-2-one in 1.5 mL of tetrahydrofuran under nitrogen at room temperature was treated with 73 mg (0.34 mmol, 1 eq.) of 3-t-butoxycarbonylamino-3-methylbutanoic acid (Example 31, Step E) followed by 94 mg (0.38 mmol, 1.1 eq.) of 2-ethoxy-1-ethoxycarbonyl-1,2-dihydroquinoline (EEDQ). Most of the solvent was evaporated under a stream of nitrogen and the resulting reaction mixture (thick syrup approx. 0.3 mL) was stirred for 3 days. The mixture was evaporated to dryness under vacuum and the residue purified by medium pressure liquid chromatography on silica, eluting with ethyl acetate/hexane (1:1) to afford 45 mg (mmol, 33%) of product. 1H NMR (200MHz, CDCl3): 1.28 (s,3H), 1.32 (s,3H), 1.35 (s,9H), 2.16 (m,2H), 2.35 (d,14Hz,1H), 2.58 (d,14Hz,1H), 2.60 (m,1H), 2.81 (m,1H), 4.70 (d,18Hz,1H), 4.99 (d,18Hz,1H), 5.37 (t,10Hz,1H), 5.83 (br s,1H), 6.98 (d,7Hz,1H), 7.05-7.45 (m,5H), 7.50-7.85 (m,3H), 8.13 (t,8Hz,1H), 8.90 (m,1H). FAB-MS: calculated for C27H35N3O4 465; found 466 (M+H)48%).

Workup

  1. customMost of the solvent was evaporated under a stream of nitrogen
  2. customthe resulting reaction mixture (thick syrup approx. 0.3 mL)
  3. customThe mixture was evaporated to dryness under vacuum
  4. customthe residue purified by medium pressure liquid chromatography on silica
  5. washeluting with ethyl acetate/hexane (1:1)
  6. customto afford 45 mg (mmol, 33%) of product

Sources & evidence

ORD record
ord-b4cdc6cfab8b4e6f9803125b20f5f40b
Source dataset
uspto-grants-1994_05
Patent number
US05310737

Reaction notes

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