1-[3-(4-Iodophenoxy)propyl]piperidine → 1'-[4-(3-piperidin-1-ylpropoxy)phenyl]-3H-spiro[2-benzofuran-1,4'-piperidine]

HRID 1095820Notes

Reaction equation

HRID 1095820 reaction equation
[NH:1]1[CH2:6][CH2:5][C:4]2([C:10]3[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=3[CH2:8][O:7]2)[CH2:3][CH2:2]1.I[C:16]1[CH:31]=[CH:30][C:19]([O:20][CH2:21][CH2:22][CH2:23][N:24]2[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]2)=[CH:18][CH:17]=1.CC(C)([O-])C.[Na+]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1>[N:24]1([CH2:23][CH2:22][CH2:21][O:20][C:19]2[CH:18]=[CH:17][C:16]([N:1]3[CH2:6][CH2:5][C:4]4([C:10]5[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=5[CH2:8][O:7]4)[CH2:3][CH2:2]3)=[CH:31][CH:30]=2)[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]1

Participants

7

Reactant 3

HCID 23047731-[3-(4-Iodophenoxy)propyl]piperidineHCID 104424983H-spiro[2-benzofuran-1,4'-piperidine]HCID 23676156Sodium t-butoxide

Product 1

HCID 667843221'-[4-(3-piperidin-1-ylpropoxy)phenyl]-3H-spiro[2-benzofuran-1,4'-piperidine]Yield 26%

Reagents, catalysts & solvents 3

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Procedure

3H-spiro[2-benzofuran-1,4′-piperidine] (131 mg, 0.695 mmol), 1-[3-(4-iodophenoxy)propyl]piperidine (200 mg, 0.58 mmol) prepared in Reference Example (2), sodium tert-butoxide (78 mg, 0.812 mmol), Pd2(dba)3 (5 mg, 0.0058 mmol), 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (7 mg, 0.0116 mmol) were mixed, and stirred overnight in 1,4-dioxane in a nitrogen atmosphere at 60° C. The reaction solution was filtered under suction through Celite, diluted with ethyl acetate, washed with water and saturated saline in that order, and the organic layer was dried with sodium sulfate. The solvent was evaporated off under reduced pressure, and the resulting residue was purified through preparative thin-layer chromatography (eluate: chloroform/methanol=10/1) to obtain the entitled compound as a colorless solid (60.5 mg, 26%).

Workup

  1. additionwere mixed
  2. filtrationThe reaction solution was filtered under suction through Celite
  3. additiondiluted with ethyl acetate
  4. washwashed with water and saturated saline in that order
  5. dry with materialthe organic layer was dried with sodium sulfate
  6. customThe solvent was evaporated off under reduced pressure
  7. customthe resulting residue was purified through preparative thin-layer chromatography (eluate: chloroform/methanol=10/1)

Sources & evidence

ORD record
ord-85842c7e911d40d3ac1a0134c2bf9bd8
Source dataset
uspto-grants-2012_03
Patent number
US08138206B2

Reaction notes

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