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ノート

反応式

HRID 975813 の反応式
[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

参加物

12

反応物 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

生成物 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

試薬・触媒・溶媒 3

HCID 3283Diethyl Ether溶媒HCID 6344Dichloromethane溶媒HCID 8471Triethylamine溶媒

実験手順

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.).

後処理

  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)

出典と根拠

ORDレコード
ord-a2384bbb1ffa436092f760bf01f3f5a5
出典データセット
uspto-grants-1997_03
特許番号
US05610154

反応ノート

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