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

HRID 1740260Notes

Reaction equation

HRID 1740260 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].Cl[C:37]([O:39][CH3:40])=[O:38].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:37]([O:39][CH3:40])=[O:38])=[CH:25][CH:26]=2)[C:10]1=[O:35])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 3

HCID 6586Methyl chloroformateHCID 8857Ethyl AcetateHCID 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 228774633(R)-t-Butoxycarbonylamino-2,3,4,5-tetrahydro-1-[[2'-[[(methoxycarbonyl)amino]methyl][1,1'-biphenyl]-4-yl]-methyl]-1H-benzazepin-2-oneYield 95%

Reagents, catalysts & solvents 2

HCID 8471TriethylamineCatalystHCID 6344DichloromethaneSolvent

Procedure

A solution of 31 mg (0.066 mmol) of the intermediate obtained in Step C in 1 mL of methylene chloride at room temperature was treated with 1 drop of triethylamine followed by 5 μL (6 mg, 0.067 mmol, 1 eq.) of methyl chloroformate. The mixture was stirred at room temperature for 1 hour then diluted into 10 mL of ethyl acetate and washed with 5% aqueous citric acid 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 5% methanol in ethyl acetate, to give 33 mg (0.062 mmol, 95%) of the product as a colorless glass. H NMR (400 MHz, CDCl3): δ 1.38 (s, 9H), 1.91 (m, 1H), 2.43-2.60 (m, 3H), 3.62 (s, 3H), 4.26 (m, 3H), 4.68 (br t, 1H), 4.93 (d, 15 Hz, 1H), 5.18 (d, 15 Hz, 1H), 5.45 (br d, 7 Hz, 1H), 7.13-7.35 (m, 11H), 7.41 (d, 8 Hz, 1H). FAB-MS: calculated for C31H35N3O5 529; found 530 (M+H, 25%), 430 (M-BOC, 100%).

Workup

  1. washwashed with 5% aqueous citric acid 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 5% methanol in ethyl acetate

Sources & evidence

ORD record
ord-0123def310214e83a59adcde89a2b960
Source dataset
uspto-grants-1999_10
Patent number
US05968924

Reaction notes

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