Trimethylsilylacetylene → 3-(4-Ethynylphenoxy)quinuclidine

HRID 1372850Notes

Reaction equation

HRID 1372850 reaction equation
I[C:2]1[CH:16]=[CH:15][C:5]([O:6][CH:7]2[CH:12]3[CH2:13][CH2:14][N:9]([CH2:10][CH2:11]3)[CH2:8]2)=[CH:4][CH:3]=1.C[Si]([C:21]#[CH:22])(C)C>CN(C=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cu]I>[C:21]([C:2]1[CH:16]=[CH:15][C:5]([O:6][CH:7]2[CH:12]3[CH2:13][CH2:14][N:9]([CH2:10][CH2:11]3)[CH2:8]2)=[CH:4][CH:3]=1)#[CH:22]

Participants

6

Reactant 2

HCID 66111TrimethylsilylacetyleneHCID 210726043-(4-Iodophenoxy)-1-azabicyclo[2.2.2]octane

Product 1

HCID 210726033-(4-Ethynylphenoxy)quinuclidine

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Procedure

Under N2, the mixture of the product from Example 1A (800 mg, 2.4 mmol), trimethylsilylacetylene (Aldrich, 392 mg, 4 mmol), Pd(PPh3)4 (Aldrich, 29 mg, 0.025 mmol) and CuI (Strem Chemicals, 10 mg, 0.05 mmol) in DMF (10 mL) was stirred at ambient temperature overnight. DMF then was removed under reduced pressure. The residue was treated with tetrabutyl ammonium fluoride (Aldrich, in THF, 1M, 5 mL) at room temperature for 3 h. The reaction was monitored with TLC. After the reaction was complete, it was diluted with EtOAc (50 mL) and washed with brine (2×10 mL). The organic solution was concentrated and the title compound was purified by chromatography (SiO2, CH2Cl2:MeOH:NH3.H2O, 90:10:1, Rf. 0.30) as a solid (560 mg, yield, 99%). 1H NMR (300 MHz, CD3OD) δ 1.42–1.54 (m, 1H), 1.61–1.87 (m, 2H), 1.93–2.07 (m, 1H), 2.10–2.18 (m, 1H), 2.71–3.00 (m, 5H), 3.19–3.37 (m, 2H), 4.49–4.56 (m, 1H), 6.86 (d, J=8.8 Hz, 2H), 7.37 (d, J=8.8 Hz, 2H) ppm. MS (DCl/NH3): m/z 228 (M+H)+.

Workup

  1. customDMF then was removed under reduced pressure
  2. additionThe residue was treated with tetrabutyl ammonium fluoride (Aldrich, in THF, 1M, 5 mL) at room temperature for 3 h
  3. additionit was diluted with EtOAc (50 mL)
  4. washwashed with brine (2×10 mL)
  5. concentrationThe organic solution was concentrated
  6. customthe title compound was purified by chromatography (SiO2, CH2Cl2:MeOH:NH3.H2O, 90:10:1, Rf. 0.30) as a solid (560 mg, yield, 99%)

Sources & evidence

ORD record
ord-827f3dfaf8134757aaa8c2d27c856502
Source dataset
uspto-grants-2007_01
Patent number
US07160876B2

Reaction notes

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