1-(4-Methoxy-benzyl)-piperidine-2,4-dione

712353-74-7

712353-75-8

A mixture of aqueous potassium carbonate (K2CO3, 3.2 g, 23.2 mmol, 5 eq.) and 18-crown-6 (purified by azeotropy with toluene, 122 mg, 0.446 mmol, 10 mol%) in anhydrous toluene (4 mL) was heated to reflux under nitrogen protection. Subsequently, a toluene solution of N-(4-methoxybenzyl)-N-(2-methoxycarbonylethyl)maleic acid methyl ester was added dropwise over 40 min. After the reflux reaction for 7 h, the reaction mixture was diluted with water (4 mL) and toluene (4 mL), cooled to 0°C and carefully acidified with 0.1 N hydrochloric acid to pH 1.7. Next, the mixture was extracted several times with dichloromethane (CH2Cl2, 3 x 80 mL), the organic phases were combined, dried, and then concentrated to give a brown oil (1.33 g). The oily substance was treated with 10% aqueous oxalic acid solution and heated to reflux for 6.5 hours. After the completion of the reaction, it was again extracted with dichloromethane (CH2Cl2) several times, and the organic phases were combined, dried and concentrated to obtain a light yellow oily crude product (1.03 g). The crude product was purified by silica gel column chromatography using a solvent mixture of dichloromethane and methanol (CH2Cl2:MeOH = 30:1) as eluent to afford 1-(4-methoxybenzyl)piperidine-2,4-dione as a light brown solid (750 mg, 69% yield). The NMR hydrogen spectrum (300 MHz, CDCl3) data were as follows: δ 2.52 (t, J = 5.7 Hz, 2H), 3.41 (s, 2H), 3.47 (t, J = 5.7 Hz, 2H), 3.80 (s, 3H), 4.62 (s, 2H), 6.16-6.88 (m, 2H), 7.20 (m, 2H).