2-(4-Bromophenyl)pyridine → 3-[2-(4-[2-Pyridyl]phenyl)ethynyl]-3-hydroxyquinuclidine

HRID 861405Notes

Reaction equation

HRID 861405 reaction equation
[C:1]([C:3]1([OH:11])[CH:8]2[CH2:9][CH2:10][N:5]([CH2:6][CH2:7]2)[CH2:4]1)#[CH:2].Br[C:13]1[CH:18]=[CH:17][C:16]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][N:20]=2)=[CH:15][CH:14]=1>C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl.[Cu]I.CN(C)C=O>[N:20]1[CH:21]=[CH:22][CH:23]=[CH:24][C:19]=1[C:16]1[CH:15]=[CH:14][C:13]([C:2]#[C:1][C:3]2([OH:11])[CH:8]3[CH2:9][CH2:10][N:5]([CH2:6][CH2:7]3)[CH2:4]2)=[CH:18][CH:17]=1

Participants

6

Reactant 2

HCID 15152372-(4-Bromophenyl)pyridineHCID 36135173-Ethynyl-1-azabicyclo[2.2.2]octan-3-ol

Product 1

HCID 197031613-[2-(4-[2-Pyridyl]phenyl)ethynyl]-3-hydroxyquinuclidine

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 3-ethynyl-3-hydroxyquinuclidine (516 mg), 2-(4-bromophenyl)pyridine (400 mg), bis(triphenylphosphine)palladium (II) chloride (100 mg), copper(I) iodide (50 mg) triethylamine (15 ml) and dimethylformamide (10 ml) was stirred at 90° C. under an atmosphere of argon for 2.5 hours. The mixture was allowed to cool to room temperature, alumina (5 g) added and the solvents removed by evaporation. This pre-absorbed material was chromatographed on alumina (30 g) using a mixture of 10% ethanol in ethyl acetate as eluent. There was thus obtained a residue which was crystallised from ethanol/hexane to give 3-[2-(4-[2-pyridyl]phenyl)ethynyl]-3-hydroxyquinuclidine as a solid, m.p. 205°-206° C.; microanalysis, found: C, 77.7; H, 6.4; N, 9.0%; C20H2ON2O.0.25H2O requires: C, 77.8; H, 6.5; N, 9.08%; NMR (DMSO-d6): 1.3(1H, m), 1.6(1H, m), 1.8-2.0(3H, m), 2.7(4H, m), 2.85(1H, d), 3.1(1H, d), 5.6(1H, s), 7.4(1H, m), 7.5(2H, d), 7.85-8.05(2H, m), 8.1(1H, d) and 8.7(1H, d); m/Z 305 (M+H).

Workup

  1. temperatureto cool to room temperature
  2. additionalumina (5 g) added
  3. customthe solvents removed by evaporation
  4. customThis pre-absorbed material was chromatographed on alumina (30 g)
  5. additiona mixture of 10% ethanol in ethyl acetate as eluent
  6. customThere was thus obtained a residue which
  7. customwas crystallised from ethanol/hexane

Sources & evidence

ORD record
ord-fed29fd8d4424231b56dbffeadc0c27f
Source dataset
uspto-grants-1998_02
Patent number
US05714496

Reaction notes

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