Hydrochloric Acid → 1-(8-Aza-bicyclo[3.2.1]oct-8-yl)-4-[4-(5-fluoro-2-methoxy-phenyl)-piperazin-1-yl]-2-phenyl-butan-1-one

HRID 975814Notes

Reaction equation

HRID 975814 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]([O:14][CH3:15])=[C:6]([N:8]2[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]2)[CH:7]=1.[CH:16]12[N:23]([C:24](=[O:35])[CH:25]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)[CH2:26][CH2:27]Cl)[CH:20]([CH2:21][CH2:22]1)[CH2:19][CH2:18][CH2:17]2.C(N(C(C)C)CC)(C)C.[I-].[K+].Cl>CN(C)C=O.CCOCC.O>[CH:20]12[N:23]([C:24](=[O:35])[CH:25]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)[CH2:26][CH2:27][N:11]3[CH2:10][CH2:9][N:8]([C:6]4[CH:7]=[C:2]([F:1])[CH:3]=[CH:4][C:5]=4[O:14][CH3:15])[CH2:13][CH2:12]3)[CH:16]([CH2:22][CH2:21]1)[CH2:17][CH2:18][CH2:19]2

Participants

9

Reactant 5

HCID 313Hydrochloric Acid2×HCID 4875Potassium IodideHCID 81531DiisopropylethylamineHCID 184141001-(5-Fluoro-2-methoxyphenyl)piperazineHCID 199683601-(8-Aza-bicyclo[3.2.1]oct-8-yl)-4-chloro-2-phenyl-butan-1-one

Product 1

HCID 199683541-(8-Aza-bicyclo[3.2.1]oct-8-yl)-4-[4-(5-fluoro-2-methoxy-phenyl)-piperazin-1-yl]-2-phenyl-butan-1-one

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Procedure

A mixture of the 4-(5-fluoro-2-methoxyphenyl)-piperazine (2.1 g, 10.0 mmole, prepared by method disclosed in U.S. Pat. No. 4,585,773), 1-(8-aza-bicyclo[3.2.1]oct-8-yl)-4-chloro-2-phenyl-butan-1-one (3.40 g, 10.0 mmole), diisopropylethylamine (1.4 g, 11.0 mmole) and potassium iodide (1.66 g, 10.0 mmole) was heated in dimethylformamide (35 mL) to 80° C. for 5 hours. After cooling to ambient temperature, the mixture was poured into water (100 mL) and extracted with ethyl acetate (2×300 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 2% methanol in ethyl acetate as eluant) followed by the treatment with 1.1 equivalent of 1N hydrogen chloride in ether gave 1.3 g of the title compound as the hydrochloride quarter hydrate, m.p. 203°-206° C.

Workup

  1. customprepared by method
  2. extractionextracted with ethyl acetate (2×300 mL)
  3. washThe combined ethyl acetate layer was washed with water (100 mL) and brine (100 mL)
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under vacuum
  7. customto give crude product
  8. customPurification of this material by column chromatoghaphy (silica gel with 2% methanol in ethyl acetate as eluant)

Sources & evidence

ORD record
ord-0cad419445674e0485777b231388dad2
Source dataset
uspto-grants-1997_03
Patent number
US05610154

Reaction notes

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