4-bromo-2-chloro-1-(2-methoxyethoxy)benzene

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 3-ethynyl-3-hydroxyquinuclidine (453 mg), methoxyethyl 4-bromo-2-chlorophenyl ether (0.97 g), bis(triphenylphosphine)palladium (II) chloride (105 mg), copper (I) iodide (55 mg), triethylamine (5 ml) and dimethylformamide (10 ml) was stirred at 70° C. under an atmosphere of argon for 2 hours. The triethylamine and dimethylformamide were removed by evaporation. The residue was purified by flash column chromatography on silica gel (Merck Art. No. 9385) using a mixture of 10% methanol in dichloromethane containing 1% ammonia (density, 0.880 g/cm3) as eluent. The residue was crystallised from acetonitrile to give 3-[2-(3-chloro-4-(2-methoxyethoxy)phenyl)ethynyl]quinuclidin-3-ol (0.52 g) as a colourless solid, m.p. 138-139° C.; microanalysis, found: C, 64.1; H, 6.7; N, 4.1%; C18H22ClNO3 requires: C, 63.9; H, 6.6; N, 4.1%; NMR ([CD3 ]2SO): 7.5(1H,d), 7.3(1H,d of d), 7.1(1H,d), 5.5(1H,s), 4.2(2H,m), 3.7(2H,m), 3.3(3H,s), 2.8(2H,m), 2.7(4H,m), 2-1.8(3H,m), 1.6(1H,m) and 1.3(1H,m); m/z 336(M+H). The triethylamine and dimethylformamide were removed by evaporation The residue was purified by flash column chromatography on silica gel (Merck Art a mixture of 10% methanol in dichloromethane containing 1% ammonia (density, 0.880 g/cm3) as eluent The residue was crystallised from acetonitrile

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 3-ethynyl-3-hydroxyquinuclidine (453 mg), methoxyethyl 4-bromo-2-chlorophenyl ether (0.97 g), bis(triphenylphosphine)palladium (II) chloride (105 mg), copper (I) iodide (55 mg), triethylamine (5 ml) and dimethylformamide (10 ml) was stirred at 70° C. under an atmosphere of argon for 2 hours. The triethylamine and dimethylformamide were removed by evaporation. The residue was purified by flash column chromatography on silica gel (Merck Art. No. 9385) using a mixture of 10% methanol in dichloromethane containing 1% ammonia (density, 0.880 g/cm3) as eluent. The residue was crystallised from acetonitrile to give 3-[2-(3-chloro-4-(2-methoxyethoxy)phenyl)ethynyl]quinuclidin-3-ol (0.52 g) as a colourless solid, m.p. 138-139° C.; microanalysis, found: C, 64.1; H, 6.7; N, 4.1%; C18H22ClNO3 requires: C, 63.9; H, 6.6; N, 4.1%; NMR ([CD3 ]2SO): 7.5(1H,d), 7.3(1H,d of d), 7.1(1H,d), 5.5(1H,s), 4.2(2H,m), 3.7(2H,m), 3.3(3H,s), 2.8(2H,m), 2.7(4H,m), 2-1.8(3H,m), 1.6(1H,m) and 1.3(1H,m); m/z 336(M+H). The triethylamine and dimethylformamide were removed by evaporation The residue was purified by flash column chromatography on silica gel (Merck Art a mixture of 10% methanol in dichloromethane containing 1% ammonia (density, 0.880 g/cm3) as eluent The residue was crystallised from acetonitrile