Triethylamine → HCID 21472416, compound

HRID 2294956Notes

Reaction equation

HRID 2294956 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].[CH3:12][C:13]([NH:15][C:16]1[CH:21]=[CH:20][C:19](I)=[CH:18][CH:17]=1)=[O:14].C(N(CC)CC)C.C(=O)([O-])[O-].[Na+].[Na+]>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=O)C>[C:13]([NH:15][C:16]1[CH:21]=[CH:20][C:19]([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)(=[O:14])[CH3:12]

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 10340Sodium CarbonateHCID 12147N-(4-Iodophenyl)acetamideHCID 36135173-Ethynyl-1-azabicyclo[2.2.2]octan-3-ol

Product 1

HCID 21472416HCID 21472416, compoundYield 31.7%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
65 °C

Procedure

A mixture of 3-ethynyl-3-hydroxyquinuclidine (302 mg), 4-iodoacetanilide (522 mg), bis(triphenylphosphine)-palladium (II) chloride (70 mg), copper (I) iodide (35 mg), triethylamine (2 ml) and DMF (4 ml) was heated at 65° C. under an atmosphere of argon for 4 hours. The reaction mixture was cooled then poured into 5% sodium carbonate solution (10 ml) and the resulting mixture extracted with ethyl acetate (3×5 ml). The organic extracts were combined, dried (MgSO4) and evaporated to give a solid residue. This residue was purified by flash column chromatography using a mixture of 10% methanol in dichloromethane containing 1% 0.880 ammonia as eluent to give 3-[2-(4-acetamidophenyl)ethynyl]-3-hydroxyquinuclidine (180 mg), m.p. 198° to 205° C. (with decomposition); microanalysis, found: C, 67.9; H, 7.0; N, 9.5%; C17H20N2O2.H2O requires: C, 67.55; H, 7.28; N, 9.27%; NMR (DMSO-d6): 1.3-1.45(1H, m), 1.56-1.7(1H, m), 1.8-2.0(3H, m), 2.06(3H, s), 2.7-2.8(4H, t), 2.85-2.92(1H, d), 3.1-3.17(1H, d), 5.65(1H, s), 7.3-7.35(2H, d), 7.55-7.6(2H, d) and 10.1(1H, br); m/Z 285 (M+H).

Workup

  1. temperatureThe reaction mixture was cooled
  2. extractionthe resulting mixture extracted with ethyl acetate (3×5 ml)
  3. dry with materialdried (MgSO4)
  4. customevaporated
  5. customto give a solid residue
  6. customThis residue was purified by flash column chromatography
  7. additiona mixture of 10% methanol in dichloromethane containing 1% 0.880 ammonia as eluent

Sources & evidence

ORD record
ord-88dcc913e6604258ae839fbf373bbc34
Source dataset
uspto-grants-1997_11
Patent number
US05691349

Reaction notes

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