Sodium Iodide → (+/-)-4-((alphaR*)-alpha-((2S*,5R*)-4-(Cyanomethyl)-2,5-dimethyl-1-piperazinyl)-3-hydroxybenzyl)-N,N-diethylbenzamide

Participants

Reaction Steps

(±)-4-((αR*)-α-((2S*,5R*)-2,5-Dimethyl-1-piperazinyl)-3-hydroxybenzyl)-N,N-diethylbenzamide, tert-butyldimethylsilyl ether (0.51 g, 1.0 mmol, Example 81, infra) was combined with 2-chloroacetonitrile (0.07 mL, 1.1 mmol, Eastman Kodak, Rochester, N.Y.) and sodium carbonate in anhydrous tetrahydrofuran. The reaction mixture was chilled in an ice bath and sodium iodide (0.16 g, 1.1 mmol) was added. The reaction was allowed to warm to room temperature and stirred overnight, The solvent was removed and the residue was redissolved in dichloromethane and washed with water. The solvent was evaporated and the residue was purified by chromatography on silica gel with ethanol (0-3%) in dichloromethane. The product was dissolved in 20 mL of acetonitrile and stirred for 3 hours with tetraethylammonium fluoride hydrate (0.18 g). The solvent was evaporated and the residue was purified by chromatography on silica gel with ethanol (0-3%) in dichloromethane. Crystallization of the product from acetonitrile gave 37 mg of solid, mp 190°-192° C. Calc for C26H34N4O4:C, 71.86; H, 7.88; N, 12.89. Found: C, 71.83; H, 7.94; N, 12.95. NMR (200 MHz, CDCl3): δ 0.93 (d, J=6 Hz, 3H); 1.15 (d, J=4.7 Hz, 3H); 1.0-1.2 (br m, 6H); 1.79 (t, J=11 Hz, 1H); 2.2-2.4 (m, 5H); 3.2-3.6 (br m, 4H); 3.36 & 3.76 (ABq, J=17.4 Hz, 2H); 5.15 (s, 1H); 6.55 (s, 1H); 6.57 (d, J=8.6 Hz, 1H); 6.73 (d, J=8 Hz, 1H); 7.13 (t, J=7.6 Hz, 1H); 7.28 & 7.42 (ABq, J=8.2 Hz, 4H).

Provenance & Evidence