Diisopropylethylamine → [(1R)-1-(N-{2-[2-(2-hydroxyethoxy)phenyl]ethyl}-N-methylcarbamoyl)-2-(2-naphthyl)ethyl]carbamic acid tert-butyl ester

HRID 366143

Reaktionsgleichung

Reaktionsgleichung von HRID 366143
[C:1]([O:5][C:6]([NH:8][C@H:9]([CH2:13][C:14]1[CH:23]=[CH:22][C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH:15]=1)[C:10]([OH:12])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].ON1C2N=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.[CH3:46][NH:47][CH2:48][CH2:49][C:50]1[CH:59]=[CH:58][CH:57]=[CH:56][C:51]=1[O:52][CH2:53][CH2:54][OH:55].C(N(C(C)C)C(C)C)C>CN(C)C=O.ClCCl.C(OCC)(=O)C>[C:1]([O:5][C:6](=[O:7])[NH:8][C@@H:9]([C:10](=[O:12])[N:47]([CH2:48][CH2:49][C:50]1[CH:59]=[CH:58][CH:57]=[CH:56][C:51]=1[O:52][CH2:53][CH2:54][OH:55])[CH3:46])[CH2:13][C:14]1[CH:23]=[CH:22][C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH:15]=1)([CH3:3])([CH3:4])[CH3:2]

Komponenten

9

Edukt 5

HCID 81531DiisopropylethylamineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 2734481(2R)-2-(((tert-butoxy)carbonyl)amino)-3-(naphthalen-2-yl)propanoic acidHCID 105840162-(2-(2-(Methylamino)ethyl)phenoxy)ethanol

Produkt 1

HCID 54188026[(1R)-1-(N-{2-[2-(2-hydroxyethoxy)phenyl]ethyl}-N-methylcarbamoyl)-2-(2-naphthyl)ethyl]carbamic acid tert-butyl esterAusbeute 52,9 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 6228DimethylformamideLösungsmittelHCID 6344DichloromethaneLösungsmittel2×HCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

(2R)-2-(tert-Butoxycarbonylamino)-3-(2-naphthyl)propionic acid (654 mg, 2.07 mmol) was dissolved in N,N-dimethylformamide (4 ml) and dichloromethane (4 ml). 1-Hydroxy-7-azabenzotriazole (282 mg, 2.07 mmol) was added. The solution was cooled to 0° C. N-(3-Dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (397 mg, 2.07 mmol) was added. The reaction mixture was stirred for 15 min at 0° C. A solution of 2-(2-(2-(methylamino)ethyl)phenoxy)ethanol (434 mg, 2.07 mmol) in dichloromethane (4 ml) and ethyldiisopropylamine (0.36 ml, 2.07 mmol) were added successively. The reaction mixture was stirred for 16 h, while it was warming up to room temperature. It was diluted with ethyl acetate (50 ml) and washed with a 10% aqueous solution of sodium hydrogen sulfate (50 ml). The aqueous phase was extracted with ethyl acetate (2×20 ml). The combined organic layers were washed with a saturated aqueous solution of sodium hydrogen carbonate (50 ml) and dried over magnesium sulfate. The solvent was removed in vacuo. The crude product was purified by flash chromatography on silica (70 g), using ethyl acetate/heptane 1:1 as eluent, to give 539 mg of [(1R)-1-(N-{2-[2-(2-hydroxyethoxy)phenyl]ethyl}-N-methylcarbamoyl)-2-(2-naphthyl)ethyl]carbamic acid tert-butyl ester.

Aufarbeitung

  1. stirringThe reaction mixture was stirred for 16 h, while it
  2. temperaturewas warming up to room temperature
  3. washwashed with a 10% aqueous solution of sodium hydrogen sulfate (50 ml)
  4. extractionThe aqueous phase was extracted with ethyl acetate (2×20 ml)
  5. washThe combined organic layers were washed with a saturated aqueous solution of sodium hydrogen carbonate (50 ml)
  6. dry with materialdried over magnesium sulfate
  7. customThe solvent was removed in vacuo
  8. customThe crude product was purified by flash chromatography on silica (70 g)

Quellen und Nachweise

ORD-Eintrag
ord-b0a6b45f07f54cdc982285b8d75f3bd9
Quelldatensatz
uspto-grants-2000_10
Patentnummer
US06127354

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