Ethyl Acetate → 3(R)-t-Butoxycarbonylamino-2,3,4,5-tetrahydro-1-[[2'-[[(benzyloxycarbonyl)amino]methyl][1,1'-biphenyl]-4-yl]methyl]-1H-benzazepin-2-one

HRID 1740261Notes

Reaction equation

HRID 1740261 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]1[CH2:15][CH2:14][C:13]2[CH:16]=[CH:17][CH:18]=[CH:19][C:12]=2[N:11]([CH2:20][C:21]2[CH:26]=[CH:25][C:24]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=3[CH2:33][NH2:34])=[CH:23][CH:22]=2)[C:10]1=[O:35])=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:36]([O:43][C:44](ON1C(=O)CCC1=O)=[O:45])[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1.ON1C2C=CC=CC=2N=N1.C(OCC)(=O)C>C(Cl)Cl.C(N(CC)CC)C>[C:1]([O:5][C:6]([NH:8][C@@H:9]1[CH2:15][CH2:14][C:13]2[CH:16]=[CH:17][CH:18]=[CH:19][C:12]=2[N:11]([CH2:20][C:21]2[CH:22]=[CH:23][C:24]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=3[CH2:33][NH:34][C:44]([O:43][CH2:36][C:37]3[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=3)=[O:45])=[CH:25][CH:26]=2)[C:10]1=[O:35])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 757711-HydroxybenzotriazoleHCID 83172Benzyl succinimido carbonateHCID 228774603(R)-t-Butoxycarbonylamino-2,3,4,5-tetrahydro-1-[[2'-aminomethyl[1,1'-biphenyl]-4-yl]methyl]-1H-benzazepin-2-one

Product 1

HCID 228774613(R)-t-Butoxycarbonylamino-2,3,4,5-tetrahydro-1-[[2'-[[(benzyloxycarbonyl)amino]methyl][1,1'-biphenyl]-4-yl]methyl]-1H-benzazepin-2-oneYield 83%

Reagents, catalysts & solvents 2

HCID 8471TriethylamineCatalystHCID 6344DichloromethaneSolvent

Procedure

A solution of 64 mg (0.14 mmol) of 3(R)-t-butoxycarbonylamino-2,3,4,5-tetrahydro-1-[[2'-aminomethyl[1,1'-biphenyl]-4-yl]methyl]-1H-benzazepin-2-one (Example 59, Step C) in 1 mL of methylene chloride at room temperature was treated with 1 drop of triethylamine followed by 36 mg (0.14 mmol, 1 eq.) of N-(benzyloxycarbonyloxy)succinimide and 5 mg of N-hydroxybenzotriazole. The mixture was stirred at room temperature for 1 hour then added to 10 mL of ethyl acetate and washed with 5% aqueous citric acid, saturated aqueous sodium bicarbonate and saturated aqueous sodium chloride. The organic layer was removed, dried over magnesium sulfate, filtered and solvents removed under vacuum. The residue was purified by medium pressure liquid chromatography on silica, eluting with ethyl acetate/hexanes (2:1), to give 68 mg (0.11 mmol, 83%) of the product as a white, crusty foam. 1H NMR (400 MHz, CDCl3): δ 1.38 (s, 9H), 1.89 (m, 1H), 2.40-2.60 (m, 3H), 4.27 (m, 3H), 4.75 (br t, 1H), 4.92 (d, 15 Hz, 1H), 5.05 (s, 2H), 5.18 (d, 15 Hz, 1H), 5.44 (br d, 7 Hz, 1H), 7.10-7.35 (m, 11H), 7.40 (d, 8 Hz, 1H). FAB-MS: calculated for C37H39N3O5 605; found 606 (M+H, 2%), 506 (M-BOC, 100%).

Workup

  1. washwashed with 5% aqueous citric acid, saturated aqueous sodium bicarbonate and saturated aqueous sodium chloride
  2. customThe organic layer was removed
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. customsolvents removed under vacuum
  6. customThe residue was purified by medium pressure liquid chromatography on silica
  7. washeluting with ethyl acetate/hexanes (2:1)

Sources & evidence

ORD record
ord-f7dd40b19fe8415784de91ae57105ed3
Source dataset
uspto-grants-1999_10
Patent number
US05968924

Reaction notes

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