Dimethylacetamide → methyl 2-[4-({(tert-butoxycarbonyl)[(1R)-1-(1-naphthyl)ethyl]amino}methyl)-3-phenylpiperidin-1-yl]-6-chloroisonicotinate

HRID 1691735Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1691735
[C:1]([O:5][C:6](=[O:33])[N:7]([C@@H:21]([C:23]1[C:32]2[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=2)[CH:26]=[CH:25][CH:24]=1)[CH3:22])[CH2:8][CH:9]1[CH2:14][CH2:13][NH:12][CH2:11][CH:10]1[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)([CH3:4])([CH3:3])[CH3:2].[Cl:34][C:35]1[CH:36]=[C:37]([CH:42]=[C:43](Cl)[N:44]=1)[C:38]([O:40][CH3:41])=[O:39].P([O-])([O-])([O-])=O.[K+].[K+].[K+].CC(N(C)C)=O>CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C.O>[C:1]([O:5][C:6]([N:7]([CH2:8][CH:9]1[CH2:14][CH2:13][N:12]([C:43]2[CH:42]=[C:37]([CH:36]=[C:35]([Cl:34])[N:44]=2)[C:38]([O:40][CH3:41])=[O:39])[CH2:11][CH:10]1[C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1)[C@@H:21]([C:23]1[C:32]2[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=2)[CH:26]=[CH:25][CH:24]=1)[CH3:22])=[O:33])([CH3:2])([CH3:3])[CH3:4]

Komponenten

7

Edukt 4

HCID 31374DimethylacetamideHCID 62657Potassium Phosphate, TribasicHCID 93237Methyl 2,6-dichloroisonicotinateHCID 59178521HCID 59178521, Verbindung

Produkt 1

HCID 86638700methyl 2-[4-({(tert-butoxycarbonyl)[(1R)-1-(1-naphthyl)ethyl]amino}methyl)-3-phenylpiperidin-1-yl]-6-chloroisonicotinateAusbeute 47,8 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418851HCID 178418851, VerbindungKatalysatorHCID 962WaterLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

A mixture of 100 mg of tert-butyl[(1R)-1-(1-naphthyl)ethyl][(3-phenylpiperidin-4-yl)methyl]carbamate, 56 mg of methyl 2,6-dichloroisonicotinate, 95 mg of potassium phosphate, 6 mg of bis(tri-tert-butylphosphine)palladium(0), and 2.0 mL of dimethylacetamide was stirred at 100° C. overnight. The reaction mixture was cooled to room temperature, and water was added thereto, followed by extraction with ethyl acetate. The organic layer was washed with saturated brine, and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane-ethyl acetate) to obtain 66 mg of methyl 2-[4-({(tert-butoxycarbonyl)[(1R)-1-(1-naphthyl)ethyl]amino}methyl)-3-phenylpiperidin-1-yl]-6-chloroisonicotinate as a pale yellow oily compound. ESI+: 614

Aufarbeitung

  1. temperatureThe reaction mixture was cooled to room temperature
  2. extractionfollowed by extraction with ethyl acetate
  3. washThe organic layer was washed with saturated brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationAfter filtration
  6. concentrationthe filtrate was concentrated under reduced pressure
  7. customThe residue was purified by silica gel column chromatography (hexane-ethyl acetate)

Quellen und Nachweise

ORD-Eintrag
ord-3c4f94d485d6490fb0162228ec89aabd
Quelldatensatz
uspto-grants-2012_04
Patentnummer
US08153658B2

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