Reaction Steps
An oven dried 250 ml 1-necked round bottomed flask was charged with cyclohexanone (26.37 g, 0.27 mol) and dry benzene (50 ml). To this solution was added pyrrolidine (29 ml, 0.35 mol) over 10 min through a dropping funnel. The resultant solution was refluxed for 3 hours with azeotroping off water and then concentrated by distilling off benzene. The remaining crude enamine was dissolved in p-dioxane (100 ml) and treated with acrylonitrile (20 ml, 0.3 mol) and refluxed for 6 hours, and then slowly treated with ethyl bromoacetate (31 ml, 0.28 mol), and refluxed for further 12 hours. Then the reaction mixture was concentrated under reduced pressure, and treated with water (30 ml) and 10% sulfuric acid (50 ml) at room temperature. The resultant solution was diluted with ether (200 ml). The organic layer was separated from the aqueous layer and further extracted twice with ether (100 ml×2), combined, and washed with saturated NaCl solution (200 ml). The resulting organic layer was dried over anhydrous magnesium sulfate, and filtered, and the solvent was removed at reduced pressure to yield a crude product. Vacuum distillation at 0.1 torr afforded the desired product 2 (37.10 g, 58%) as a mixture of cis and trans stereoisomers: bp 160°-175° C. (0.1 torr); FT-IR (neat, cm-1) 2936, 2861, 2245, 1732, 1710, 1449, 1376, 1344, 1276, 1234, 1188, 1116, 1071, 1028, 989, 947, 862, 838, 748; 1H NMR (CDCl3, 400 MHz) δ 4.14 (q, J=7.1 Hz, 2H), 2.92 (m, 1H), 2.75 (dd, 16.6, 7.2 Hz, 1H), 2.56 (m, 1H), 2.45 (t, J=7.4 Hz, 1H), 2.43 (t, J=7.5 Hz, 1H), 2.17 (dd, J=16.6, 5.7 Hz, 2H), 2.22-2.05 (m, 2H), 1.96-1.78 (m, 2H), 1.55 (ddd, J=17.4, 8.8, 4.7 Hz, 1H), 1.42 (m, 2H), 1.26 (t, J=7.2 Hz, 3H); 13C NMR (CDCl3, 100 MHz) δ 210.92, 172.22, 119.63, 48.92, 48.81, 47.35 (47.14 for minor), 34.80, 34.55, 34.25, 34.13, 4.93, 15.09 (14.07 for minor); MS (El, 70 eV, rel. intensity) 237 (M, 17), 208(12), 192(B), 191(59), 163(27), 150(58), 141(35), 95(20), 84(27), 67(13), 55(20), 49(14); HRMS (El) calcd. for C13H19NO3 237.1365. Found 237.1361.
