Allyl bromide → (+/-)-4-(alpha-(trans-4-allyl-2,5-dimethyl-1-piperazinyl)-5-(tert-butyldimethylsilyloxy)-2-fluorobenzyl)-N,N-diethylbenzamide

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Reaction Steps

The benzhydrylpiperazine from above (0.44 g, 0.83 mmol) was treated with allyl bromide (0.074 mL, 0.85 mmol) and anhydrous sodium carbonate (0.44 g, 4.2 mmol) as in Example 1. The product was purified by preparative thin layer chromatography (silica gel with dichloromethane:methanol:ammonium hydroxide/90:10:1) to give 0.37 g (78%) of (±)-4-(α-(trans-4-allyl-2,5-dimethyl-1-piperazinyl)-5-(tert-butyldimethylsilyloxy)-2-fluorobenzyl)-N,N-diethylbenzamide as a yellow oil. Reaction with tetraethylammonium fluoride hydrate in acetonitrile as in Example 1, followed by chromatography on silica gel with dichloromethane:methanol/4:1 gave 0.24 g (77%) of (±)-4-α-(trans-4-allyl-2,5-dimethyl-1-piperazinyl)-2-fluoro-5-hydroxybenzyl)-N,N-diethylbenzamide as a light amber resin. NMR (CDCl3): δ 1.0-1.3 (m, 12H); 2.0-2.3 (m, 2H); 2.5-3.05 (m, 5H); 3.2-3.6 (br m, 5H); 5.1-5.3 (m, 2H); 5.25 and 5.55 (s, 1H); 5.7-6.0 (m, 1H); 6.5-7.2 (m, 3H); 7.25 (d, J=8 Hz, 2H); 7.4 (d, J=8 Hz, 2H). A solution of the product in absolute ethanol was titrated to pH 4 with ethanolic hydrochloric acid, concentrated and treated with diethyl ether to precipitate 0.21 g (63%) of the monohydrochloride as an off-white powder. Calc. for C27H36FN3O2HCl 1.25 H2O: C, 63.27; H, 7.77; N, 8.20; Cl, 6.92. Found: 63.33; H, 7.78; N, 8.24; Cl, 7.00. Mass spectrum (Cl--CH4) m/z: 454 (M+1, 100%), 453 (M, 6%), 300 (17%), 153 (95%).

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