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Dichloromethane → 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 1379886
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Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 1379886
[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].C(Cl)Cl.Cl[C:40]([O:42][CH3:43])=[O:41]>C(N(CC)CC)C.C(OCC)(=O)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:40]([O:42][CH3:43])=[O:41])=[CH:25][CH:26]=2)[C:10]1=[O:35])=[O:7])([CH3:4])([CH3:2])[CH3:3]
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Komponenten

6

Edukt 3

HCID 6344DichloromethaneHCID 6586Methyl chloroformateHCID 228774603(R)-t-Butoxycarbonylamino-2,3,4,5-tetrahydro-1-[[2'-aminomethyl[1,1'-biphenyl]-4-yl]methyl]-1H-benzazepin-2-one

Produkt 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-oneAusbeute 95 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 8471TriethylamineKatalysatorHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

A solution of 31 mg (0.066 mmol) of the intermediate obtained in Step C in I 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. 1H 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%).

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-1dbdbecc8f8e43f392d5a5f9fb80d7a4
Quelldatensatz
uspto-grants-1997_09
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US05672596

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