Reaction Steps
A 200-mL, three-necked, round-bottomed flask was equipped with a magnetic stirrer, a heating mantle, a standard condenser with a N2 inlet, a 50-mL addition funnel, and a glass stopper. A mixture containing 3,4-dimethoxybenzylamine (8.36 g, 50 mmol), paraformaldehyde (3.15 g, 105 mmol) and CH3OH (35 mL) was made acidic with the addition of glacial acetic acid (3.0 g, 50 mmol). Stirring the mixture under N2 for 20 min was followed by the dropwise addition of 1-isopropyl-4-piperidinone (42, 7.06 g, 50 mmol) and glacial acetic acid (3.0 g, 50 mmol) in CH3OH (25 mL) over 1.25 h. Boiling of the mixture was continuous for an additional 23 h. This new mixture was evaporated to give a red viscous oil. After dissolving the oil in H2O (100 mL), the solution was extracted (ether, 2×100 mL), the latter being discarded. Chilling (ice water bath) of the water layer below 10° C., followed by basification (pH~12) with KOH pellets (6.6 g, 100 mmol), produced an orange suspension which was extracted (CH2Cl2, 4×80 mL). Combined extracts were dried (Na2SO4, overnight), filtered, and concentrated to give a crude oil. This oil was digested in 250 mL of Skelly B (bp 60°-68° C.) for 0.5 h and the supernatant was decanted. Evap-oration of the solvent gave an oil which, when distilled (175°-205° C./10-4 mm Hg), afforded a yellow oil. Adding Skelly B induced crystallization to give 4.32 g (26%) of off white ketone (23); mp 79.5°-80.5° C. IR (KBr) cm-1 3095, 3015 (Ar--H), 2980, 2955, 2920, 2855, 2810 (C--H), 1745 (C=O), 1620, 1605 (C=C); 1H NMR (DCCl3) δ1.03 (d, 6 H, CH3, J=6.6 Hz), 2.59 [bs, 2 H, H(1,5)], 2.81-2.90 [m, 5 H, ring protons and CH(CH3)2 ], 2.98 (dd, 2 H, ring protons, J=10.7 Hz, J'=3.2 Hz), 3.08 (dd, 2 H, ring protons, J=10.7 Hz, J'=2.99 Hz), 3.47 (s, 2 H, ArCH2), 3.87 (s, 3 H, OCH3), 3.88 (s, 3 H, OCH3), 6.80-6.92 (m, 3 H, Ar--H); 13C NMR (DCCl3) ppm 18.17 (CH3), 46.85 [C(1,5)], 53.40 [CH(CH3)2 ], 53.86 [C(2,4)], 55.76, 55.86 (OCH3), 58.01 [C(6,8)], 60.93 (ArCH2), 110.60, 111.46, 120.68 131.30, 148.04, 148.90 (Ar--C), 215.27 (C=O); 15N NMR (DCCl3) ppm 39.66 [N(7)], 40.93 [N(3)]. Anal. Calcd. for C19H28N2O3 : C, 68.65; H, 8.49. Found: C, 68.70; H, 8.53.
