海萝胶 → 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

反应方程式

HRID 975813 反应方程式
[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

参与物

12

反应物 8

HCID 313海萝胶HCID 14798二甲基对苯二胺二盐酸HCID 637985降莨菪鹼HCID 637986TropaneHCID 27239391-乙基-(3-二甲基氨基丙基)碳酰二亚胺盐酸盐HCID 98634284-[4-(2-Methoxyphenyl)piperazin-1-yl]-2-phenylbutanoic acidHCID 105593693-乙酰莨菪烷HCID 21226127Hydrate;dihydrochloride

产物 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

试剂、催化剂与溶剂 3

HCID 3283乙醚溶剂HCID 6344二氯甲烷溶剂HCID 8471三乙胺溶剂

实验过程

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.).

后处理

  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)

来源与证据

ORD记录
ord-a2384bbb1ffa436092f760bf01f3f5a5
来源数据集
uspto-grants-1997_03
专利号
US05610154

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