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 1591462Notes

Reaction equation

HRID 1591462 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-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-1,2dihydroquinoline (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 (200 MHz, CDCl3): 1.28 (s,3H), 1.32 (s,3H), 1.35 (s,9H), 2.16 (m,2H), 2.35 (d,14 Hz,1H), 2.58 (d,14 Hz,1H), 2.60 (m,1H), 2.81 (m,1H), 4.70 (d,18 Hz,1H), 4.99 (d,18 Hz,1H), 5.37 (t,10 Hz,1H), 5.83 (br s,1H), 6.98 (d,7 Hz,1H), 7.05-7.45 (m,5H), 7.50-7.85 (m,3H), 8.13 (t,8 Hz,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-1d8954a17de041f7a175182f8f829050
Source dataset
uspto-grants-1993_04
Patent number
US05206235

Reaction notes

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