Hydrochloric Acid → (S)-4-Benzyloxy-2-{2-[(2-tert-butoxycarbonyl-ethyl)-(3,4-dichloro-phenyl)-amino]-ethylamino}-butyric Acid methyl ester

HRID 1096198Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1096198
[C:1]([O:5][C:6](=[O:21])[CH2:7][CH2:8][N:9]([C:13]1[CH:18]=[CH:17][C:16]([Cl:19])=[C:15]([Cl:20])[CH:14]=1)[CH2:10][CH:11]=O)([CH3:4])([CH3:3])[CH3:2].[CH3:22][O:23][C:24](=[O:37])[C@@H:25]([NH2:36])[CH2:26][CH2:27][O:28][CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1.Cl.C(N(CC)CC)C.B.N1C=CC=CC=1>ClCCCl.CCO.CC(O)=O>[CH3:22][O:23][C:24](=[O:37])[C@@H:25]([NH:36][CH2:11][CH2:10][N:9]([CH2:8][CH2:7][C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:21])[C:13]1[CH:18]=[CH:17][C:16]([Cl:19])=[C:15]([Cl:20])[CH:14]=1)[CH2:26][CH2:27][O:28][CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1

Komponenten

8

Edukt 5

HCID 313Hydrochloric Acid2×HCID 8471TriethylamineHCID 2723995Borane;pyridineHCID 66782701(S)-2-amino-4-benzyloxy-butyric acid methyl esterHCID 866383783-[(3,4-Dichloro-phenyl)-(2-oxo-ethyl)-amino]-propionic Acid tert-butyl ester

Produkt 1

HCID 66782973(S)-4-Benzyloxy-2-{2-[(2-tert-butoxycarbonyl-ethyl)-(3,4-dichloro-phenyl)-amino]-ethylamino}-butyric Acid methyl esterAusbeute 92 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 176Acetic AcidLösungsmittelHCID 229016121,2-Dichloroethane ethanolLösungsmittel

Versuchsvorschrift

6.26 g (18.83 mmol) of 3-[(3,4-dichloro-phenyl)-(2-oxo-ethyl)-amino]-propionic acid tert-butyl ester and 4.89 g (18.83 mmol) of (S)-2-amino-4-benzyloxy-butyric acid methyl ester; hydrochloride (intermediate 5) were dissolved in DCE:EtOH (1:1, 134 ml) and treated slowly with 3.15 ml (18.83 mmol) of triethylamine, 4.94 ml of AcOH and 4.94 ml (39.55 mmol, 8 M in pyridine) of pyridine-borane complex (cooling with a water bath to RT). The reaction was stirred at RT over 1 h, then partitioned between aq. NaHCO3 solution and EtOAc (3×). The organic phases were washed with aq. sat. NaHCO3 solution, aq. 10% NaCl solution, dried over Na2SO4 evaporated and purified by flash silica gel column (CH2Cl2:MeOH 99:1) to yield 9.35 g (92%) of the title compound as yellow oil. MS: 539.5 (MH+, 2Cl).

Aufarbeitung

  1. custompartitioned between aq. NaHCO3 solution and EtOAc (3×)
  2. washThe organic phases were washed with aq. sat. NaHCO3 solution, aq. 10% NaCl solution
  3. dry with materialdried over Na2SO4
  4. customevaporated
  5. custompurified by flash silica gel column (CH2Cl2:MeOH 99:1)

Quellen und Nachweise

ORD-Eintrag
ord-98d5203bf59b44cc992c24d3456f010b
Quelldatensatz
uspto-grants-2012_03
Patentnummer
US08138175B2

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