Reaction Steps
To a solution of alcohol (Example 1, 0.78 g, 1:1 mixture of stereoisomers) was added 0.5M-potassium hexamethyldisilazide (5.84 ml, in toluene). After 1 h, 3,5-dimethylbenzyl bromide (0.58 g) was added for 3 h. The solution was evaporated to dryness after a further 3 h, and the residue partitioned between dichloromethan and water. The organic phase was dried (MgSO4), evaporated and purified by column chromatography on silica gel eluting with petroleum ether (bp 6014 80) containing increasing amounts of ethyl acetate (50% to 100%) and then methanol/ethyl acetate (15:85) to give a single diastereomer of the title compound. This was crystallised by addition of oxalic acid (72 mg) in propan-2-ol and diethyl ether to give 3-[(3,5-dimethylphenyl)methyloxy]-2-(1,2-diphenylethyl)-1-azabicyclo[2.2.2]octane hydrogen oxalate salt isomer A mp 64°-66° C.1HNMR(DMSO,360MHz)δ 7.2-6.6 (13H,m,aryl), 4.6 (1H, d, J=16.0 Hz, OCHAHB),4.4 (1H, d, J=16.0 Hz, OCHAHB),3.5 (1H, m, OCHCH),3.3 (1H, m, NCHAHB), 2.99 (1H, dd, NCHCH)),2.8-2.60 (5H, m, NCHAHB,NCH2,PhCH2), 2.4(1H,m,PhCHCH2),2.3 (6H, s, CH3, CH3),2.25 (1H, m, bridgehead CH),1.9 (1H, m, NCH2CHAHB),1.65 (1H, m, NCH2CHAHB), 1.46-1.22 (2H, m, NCH2CH2); Found C, 71.09; H, 6.84; N, 2.51. C30H35NO.C2H2O4.0.3H2O requires C, 71.19;H,6.86;N,2.67.m/e (EI) 425(M+), (CI+)426 (M+H), (CI-=)424 (M-H).
