Diisopropylethylamine → N-((1R)-1-(N-(2-(2-(2-hydroxyethoxy)phenyl)ethyl)-N-methylcarbamoyl)-2-(2-naphthyl)ethyl)-N-methylcarbamic acid tert-butyl ester

HRID 650819

Reaktionsgleichung

Reaktionsgleichung von HRID 650819
Cl.CN(C)CCCN=C=NCC.[C:13]([O:17][C:18]([N:20]([C@H:22]([CH2:26][C:27]1[CH:36]=[CH:35][C:34]2[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=2)[CH:28]=1)[C:23]([OH:25])=O)[CH3:21])=[O:19])([CH3:16])([CH3:15])[CH3:14].ON1C2N=CC=CC=2N=N1.[CH3:47][NH:48][CH2:49][CH2:50][C:51]1[CH:60]=[CH:59][CH:58]=[CH:57][C:52]=1[O:53][CH2:54][CH2:55][OH:56].C(N(C(C)C)C(C)C)C>CN(C)C=O.ClCCl.C(OCC)(=O)C>[C:13]([O:17][C:18](=[O:19])[N:20]([C@@H:22]([C:23](=[O:25])[N:48]([CH2:49][CH2:50][C:51]1[CH:60]=[CH:59][CH:58]=[CH:57][C:52]=1[O:53][CH2:54][CH2:55][OH:56])[CH3:47])[CH2:26][C:27]1[CH:36]=[CH:35][C:34]2[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=2)[CH:28]=1)[CH3:21])([CH3:16])([CH3:15])[CH3:14]

Komponenten

9

Edukt 5

HCID 81531DiisopropylethylamineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 10065151(2R)-2-[methyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]-3-naphthalen-2-ylpropanoic acidHCID 105840162-(2-(2-(Methylamino)ethyl)phenoxy)ethanol

Produkt 1

HCID 53783076N-((1R)-1-(N-(2-(2-(2-hydroxyethoxy)phenyl)ethyl)-N-methylcarbamoyl)-2-(2-naphthyl)ethyl)-N-methylcarbamic acid tert-butyl esterAusbeute 69,2 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 6228DimethylformamideLösungsmittelHCID 6344DichloromethaneLösungsmittel2×HCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

At 0° C. N-(3-Dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (558 mg, 2.91 mmol) was given to a solution of (2R)-2-(N-(tert-butoxycarbonyl)-N-methylamino)-3(2-naphthyl)propionic acid (959 g, 2.91 mmol) and 1-Hydroxy-7-azabenzotriazole (396 mg, 2.91 mmol) in N,N-dimethylformamide (5 ml) and dichloromethane (5 ml). The solution was stirred for 20 min at 0° C. A solution of 2-(2-(2-(Methylamino)ethyl)phenoxy)ethanol (608 mg, 2.91 mmol) in dichloromethane (5 ml) and ethyldiisopropylamine (0.50 ml, 2.91 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 (150 ml) and washed with a 10% aqueous sodium hydrogen sulfate solution (70 ml). The aqueous phase was extracted with ethyl acetate (2×30 ml). The combined organic layers were washed with saturated sodium hydrogen carbonate soltuion (150 ml) and dried over magnesium sulfate. The solvent was removed in vacuo. The crude product was purified by flash chromatography on silica (110 g), using ethyl acetate/heptane (1: 1) as eluent, to give 1.02 g of N-((1R)-1-(N-(2-(2-(2-hydroxyethoxy)phenyl)ethyl)-N-methylcarbamoyl)2-(2-naphthyl)ethyl)-N-methylcarbamic acid tert-butyl ester.

Aufarbeitung

  1. customAt 0° C
  2. stirringThe reaction mixture was stirred for 16 h, while it
  3. temperaturewas warming up to room temperature
  4. washwashed with a 10% aqueous sodium hydrogen sulfate solution (70 ml)
  5. extractionThe aqueous phase was extracted with ethyl acetate (2×30 ml)
  6. washThe combined organic layers were washed with saturated sodium hydrogen carbonate soltuion (150 ml)
  7. dry with materialdried over magnesium sulfate
  8. customThe solvent was removed in vacuo
  9. customThe crude product was purified by flash chromatography on silica (110 g)

Quellen und Nachweise

ORD-Eintrag
ord-33b9ed1e2fc541d4996c19461f655243
Quelldatensatz
uspto-grants-2001_08
Patentnummer
US06274584B1

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