Hydrochloric Acid → 4-[4-(2-Methoxy-phenyl)-piperazin-1-yl]-2-phenyl-1(1,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-butan-1-one

HRID 975819Notes

Reaction equation

HRID 975819 reaction equation
[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](O)=[O:19])[CH2:11][CH2:10]1.[CH3:27][C:28]12[CH2:35][CH:32]([NH:33][CH2:34]1)[CH2:31][C:30]([CH3:37])([CH3:36])[CH2:29]2.Cl.CN(C)CCCN=C=NCC.C(N(CC)CC)C.[OH-].[Na+].Cl>C(Cl)Cl.CCOCC>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[N:9]1[CH2:10][CH2:11][N:12]([CH2:15][CH2:16][CH:17]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[C:18]([N:33]2[CH2:34][C:28]3([CH3:27])[CH2:35][CH:32]2[CH2:31][C:30]([CH3:37])([CH3:36])[CH2:29]3)=[O:19])[CH2:13][CH2:14]1

Participants

9

Reactant 6

HCID 313Hydrochloric Acid2×HCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 1037871,3,3-Trimethyl-6-azabicyclo(3.2.1)octaneHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 98634284-[4-(2-Methoxyphenyl)piperazin-1-yl]-2-phenylbutanoic acid

Product 1

HCID 199683574-[4-(2-Methoxy-phenyl)-piperazin-1-yl]-2-phenyl-1(1,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-butan-1-oneYield 47%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of 4-[4-(2-methoxyphenyl) piperazin-1-yl]-2-phenylbutanoic acid (1.70 g, 5.0 mmole), 1,3,3-trimethyl-6-azabicyclo[3.2.1]-octane (0.77 g, 5.0 mmole), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.96 g, 5.0 mmole) and triethylamine (0.55 g, 5.0 mmole) in methylene chloride (10 mL) was stirred at ambient temperature for 48 hr. The mixture was poured into 1N sodium hydroxide (75 mL) and extracted with ethyl acetate (3×75 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. This material was treated with 1.1 equivalent of 1N hydrogen chloride in ether (100 mL) to give 1.15 g of the title compound as the hydrochloride sequihydrate, m.p. 110°-145° C. (dec.).

Workup

  1. extractionextracted with ethyl acetate (3×75 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

Sources & evidence

ORD record
ord-6d14e0d9ea4149c8a12970353c0a690a
Source dataset
uspto-grants-1997_03
Patent number
US05610154

Reaction notes

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