Trimethylsilylacetylene → 3-(4-Ethynylphenoxy)quinuclidine

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)+.

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%)

ORD record

ord-827f3dfaf8134757aaa8c2d27c856502

Source dataset

uspto-grants-2007_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07160876B2