Hydrochloric Acid → HCID 9817140, compound

Participants

Reaction Conditions

Reaction Steps

A solution of sec-butyllithium in cyclohexane (100 ml, 1.3M) was added dropwise with stirring to a solution of 4-bromobiphenyl (25 g) in dry tetrahydrofuran (240 ml) under an argon atmosphere at -78° C. The mixture was stirred for 5 minutes and a solution of quinuclidin-3-one (12 g) in dry tetrahydrofuran (100 ml) added during 20 minutes. Stirring was continued at -78° C. for 30 minutes and the mixture allowed to reach room temperature over 2 hours. 2M Hydrochloric acid (225 ml) was added keeping the reaction temperature below 10° C. The aqueous layer was separated and washed with diethyl ether (2×300 ml) before the addition of excess sodium hydroxide solution (density 1.35 g/cm3) to pH14. The mixture was extracted with ethyl acetate which had been heated to 50° C. and the ethyl acetate phase separated, dried (Na2SO4) and evaporated to yield a colourless solid which crystallised from ethyl acetate to give 3-(biphenyl-4-yl)-3-hydroxyquinuclidine (11.0 g) m.p. 165°-166° C.; microanalysis, found: C, 81.1; H, 7.5; N, 5.2%; C19H21NO 0.1H2O requires: C, 81.1; H, 7.5; N, 5.0%; NMR (CDCl3 /CD3CO2D): 1.7-1.9(3H, m,), 2.5(1H, m), 2.5-2.7(1H, m), 3.2-3.5(4H, m), 3.7(1H, dd), 4.0(1H, dd) and 7.3-7.7(9H, m); m/z 279 (M+).

Provenance & Evidence