N-Methyl-3-phenylpropan-1-amine → N-Methyl-N-((1R)-1-(N-methyl-N-(3-phenylpropyl)carbamoyl)-2-(2-naphthyl)ethyl)carbamic acid tert-butyl ester

HRID 366119

Reaktionsgleichung

Reaktionsgleichung von HRID 366119
[C:1]([O:5][C:6]([N:8]([C@H:10]([CH2:14][C:15]1[CH:24]=[CH:23][C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[CH:16]=1)[C:11](O)=[O:12])[CH3:9])=[O:7])([CH3:4])([CH3:3])[CH3:2].ON1C2N=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.[CH3:47][NH:48][CH2:49][CH2:50][CH2:51][C:52]1[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=1.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])[N:8]([CH3:9])[C@@H:10]([C:11](=[O:12])[N:48]([CH3:47])[CH2:49][CH2:50][CH2:51][C:52]1[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=1)[CH2:14][C:15]1[CH:24]=[CH:23][C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[CH:16]=1)([CH3:2])([CH3:3])[CH3:4]

Komponenten

9

Edukt 5

HCID 35417N-Methyl-3-phenylpropan-1-amineHCID 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 acid

Produkt 1

HCID 54207130N-Methyl-N-((1R)-1-(N-methyl-N-(3-phenylpropyl)carbamoyl)-2-(2-naphthyl)ethyl)carbamic acid tert-butyl esterAusbeute 46,3 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 6228DimethylformamideLösungsmittelHCID 6344DichloromethaneLösungsmittel2×HCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

(2R)-2-(N-(tert-Butoxycarbonyl)-N-methylamino)-3-(2-naphthyl)propionic acid (2.21 g, 6.70 mmol) was dissolved in N,N-dimethylformamide (3 ml) and dichloromethane (6 ml). 1-Hydroxy-7-azabenzotriazole (0.91 g, 6.70 mmol) was added. The solution was cooled to 0° C. N-(3-Dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (1.28 g, 6.70 mmol) was added. The reaction mixture was stirred for 15 min at 0° C. A solution of N-methyl-N-(3-phenylpropyl)amine (1.0 g, 6.7 mmol) in dichloromethane (3 ml) was added. Ethyldiisopropylamine (1.2 ml, 6.7 mmol) was added. The reaction mixture was stirred for 16 h, while it was slowly warming up to room temperature. The solution was diluted with ethyl acetate (100 ml). It was washed with 1 N hydrochloric acid (100 ml). The aqueous phase was extracted with ethyl acetate (100 ml). The combined organic layers were washed with saturated sodium hydrogen carbonate solution (100 ml) and dried over magnesium sulfate. The solvent was removed in vacuo. The crude product was purified by flash chromatography on silica (400 g), using ethyl acetate/heptane (1:3) as eluent to give 1.43 g of N-methyl-N-((1R)-1-(N-methyl-N-(3-phenylpropyl)carbamoyl)-2-(2-naphthyl)ethyl)carbamic acid tert-butyl ester.

Aufarbeitung

  1. stirringThe reaction mixture was stirred for 16 h, while it
  2. temperaturewas slowly warming up to room temperature
  3. washIt was washed with 1 N hydrochloric acid (100 ml)
  4. extractionThe aqueous phase was extracted with ethyl acetate (100 ml)
  5. washThe combined organic layers were washed with saturated sodium hydrogen carbonate solution (100 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 (400 g)

Quellen und Nachweise

ORD-Eintrag
ord-f6113c781e474e0fab3d552a2fd2ac73
Quelldatensatz
uspto-grants-2000_10
Patentnummer
US06127354

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