Chloride → HCID 21472389, compound

HRID 2294970Notes

Reaction equation

HRID 2294970 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].[CH2:12]([O:17][C:18]1[CH:23]=[CH:22][C:21](I)=[CH:20][CH:19]=1)[CH2:13][CH2:14][CH2:15][CH3:16].[Cl-].[OH-].[Na+]>O.C1(C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)[Pd][P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I.CN(C)C=O.C(N(CC)CC)C>[CH2:12]([O:17][C:18]1[CH:19]=[CH:20][C:21]([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:22][CH:23]=1)[CH2:13][CH2:14][CH2:15][CH3:16]

Participants

10

Reactant 4

HCID 312ChlorideHCID 14798Sodium HydroxideHCID 36135173-Ethynyl-1-azabicyclo[2.2.2]octan-3-olHCID 21472391HCID 21472391, compound

Product 1

HCID 21472389HCID 21472389, compoundYield 61.1%

Reagents, catalysts & solvents 5

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178419050HCID 178419050, compoundCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

A mixture of 3-ethynyl-3-hydroxyquinuclidine (750 mg), 4-n-pentyloxyiodobenzene (1.45 g), bis(triphenylphosphine)-palladium. (II) chloride (175 mg), copper (I) iodide (90 mg), triethylamine (5 ml) and dimethylformamide (10 ml) was stirred at 80° C. under an atmosphere of argon for 4 hours. The mixture was cooled, diluted with water (50 ml) and basified with 2M aqueous sodium hydroxide solution (10 ml). The mixture was extracted with ethyl acetate containing 10% methanol (3×30 ml). The organic extracts were combined, and filtered through a short column of silica gel (Varian Bond--elut S1 silica gel). The eluent was evaporated and the residue was crystallised from acetonitrile to give 3-[2-(4-n-pentyloxyphenyl)ethynyl]-3-hydroxyquinuclidine (950 mg) as a solid, m.p. 153°-154° C.; microanalysis, found: C, 76.4; H, 8.9; N, 4.4%; C20H27NO2 requires: C, 76.6; H, 8.68; N, 4.47%; NMR: 0.82-0.95(3H,t), 1.22-1.48(5H,m), 1.6-1.76(3H,m), 1.8-2.0(3H,m), 2.6-2.9(6H,m), 3.9-4.0(2H,t), 5.5(1H,s), 6.85-6.95(2H,d), 7.3-7.4(2H,d); m/z 314(M+H).

Workup

  1. temperatureThe mixture was cooled
  2. extractionThe mixture was extracted with ethyl acetate containing 10% methanol (3×30 ml)
  3. filtrationfiltered through a short column of silica gel (Varian Bond--elut S1 silica gel)
  4. customThe eluent was evaporated
  5. customthe residue was crystallised from acetonitrile

Sources & evidence

ORD record
ord-395bc950a5214f6ebb18b0b6842901a4
Source dataset
uspto-grants-1997_11
Patent number
US05691349

Reaction notes

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