Hydrochloric Acid → 1-(8-Aza-bicyclo[3.2.1]oct-8-yl)-4-[4-(2-methoxy-phenyl)-piperazin-1-yl]-2-phenyl-butan-1-one

HRID 975813

Reaktionsgleichung

Reaktionsgleichung von HRID 975813
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[N:9]1[CH2:14][CH2:13][N:12]([CH2:15][CH2:16][CH:17]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[C:18]([OH:20])=O)[CH2:11][CH2:10]1.[C@@H:27]12[NH:34][C@@H:31]([CH2:32][CH2:33]1)[CH2:30][CH2:29][CH2:28]2.[C@@H]12N(C)[C@@H](CC1)CCC2.CC(OC1C[C@H]2N(C)[C@H](CC2)C1)=O.Cl.CN(C)CCCN=C=NCC.[OH-].[Na+].Cl.O.Cl.Cl>C(Cl)Cl.CCOCC.C(N(CC)CC)C>[CH:31]12[N:34]([C:18](=[O:20])[CH:17]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[CH2:16][CH2:15][N:12]3[CH2:11][CH2:10][N:9]([C:4]4[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=4[O:2][CH3:1])[CH2:14][CH2:13]3)[CH:27]([CH2:33][CH2:32]1)[CH2:28][CH2:29][CH2:30]2

Komponenten

12

Edukt 8

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 637985(1R,5S)-8-Azabicyclo[3.2.1]octaneHCID 637986TropaneHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 98634284-[4-(2-Methoxyphenyl)piperazin-1-yl]-2-phenylbutanoic acidHCID 105593693-AcetyltropineHCID 21226127Hydrate;dihydrochloride

Produkt 1

HCID 199683561-(8-Aza-bicyclo[3.2.1]oct-8-yl)-4-[4-(2-methoxy-phenyl)-piperazin-1-yl]-2-phenyl-butan-1-one

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 3283Diethyl EtherLösungsmittelHCID 6344DichloromethaneLösungsmittelHCID 8471TriethylamineLösungsmittel

Versuchsvorschrift

A mixture of 4-[4-(2-methoxyphenyl)piperazin-1-yl]-2-phenylbutanoic acid (4.0 g, 11.3 mmole), desmethyltropane (1.7 g, 15.3 mmole, prepared from tropane by the method used by R. A. Olofson et. al., J. Org. Chem., 1984, 49(11), 2081, for the conversion of O-acetyltropine to O-acetyldesmethyltropine), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (2.2 g, 11.3 mmole) and triethylamine (0.19.8 mmole) in methylene chloride (25 mL) was stirred at ambient temperature for 48 hr. The mixture was poured into 1 N sodium hydroxide (100 mL) and extracted with ethyl acetate (3×100 mL). The combined ethyl acetate layer was washed with water (100 mL) and brine (100 mL), dried over anhydrous magnesium sulfate, filtered and concentrated under vacuum to give crude product. Purification of this material by column chromatoghaphy (silica gel with 1% ammonia in ethyl acetate as eluant) followed by the treatment with 1.1 equivalent of 1N hydrogen chloride in ether gave 2.5 g of the title compound as the hydrochloride hemihydrate, m.p. 225°-228° C. (dec.).

Aufarbeitung

  1. extractionextracted with ethyl acetate (3×100 mL)
  2. washThe combined ethyl acetate layer was washed with water (100 mL) and brine (100 mL)
  3. dry with materialdried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under vacuum
  6. customto give crude product
  7. customPurification of this material by column chromatoghaphy (silica gel with 1% ammonia in ethyl acetate as eluant)

Quellen und Nachweise

ORD-Eintrag
ord-a2384bbb1ffa436092f760bf01f3f5a5
Quelldatensatz
uspto-grants-1997_03
Patentnummer
US05610154

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