Palmitoylethanolamide

141-43-5

57-10-3

544-31-0

1) Under nitrogen protection, triethylamine (2 mL) was slowly added dropwise to a reaction vessel containing mercaptomethyl resin (2 g, MATRIX-INN), N-hydroxymaleimide (1.1 g, 9.7 mmol) and DMF (40 mL). After stirring at room temperature for 24 hours, the temperature was raised to 55°C and stirring was continued for 4 hours. The reaction mixture was cooled to room temperature and filtered, and the resulting NHS resin was washed twice each with DMF, distilled water and isopropanol sequentially, and dried under vacuum. 2) Palmitic acid (1.465 g, 5.72 mmol), NHS resin (1.50 g) prepared above, DIC (diisopropylcarbodiimide, 0.72 g, 5.72 mmol) and triethylamine (2 mL) were suspended in dichloromethane (15 mL). After stirring for 4 h at room temperature, the filtrate was filtered and retained for subsequent reactions (the amount of palmitic acid, DIC and solvent in the filtrate was detected by HPLC). The resin was washed twice each with DMF, water, isopropanol and dichloromethane sequentially, and dried under vacuum to obtain 1.70 g of dried resin with a loading of 1.0 mmol/g of immobilized palmitic acid active ester. 3) Ethanolamine (93.2 mg, 1.58 mmol) was added to a flask containing the activated ester (1.75 g) and 50 mL of ethanol, and suspended and stirred for 0.5 hr. The solid resin was removed by centrifugation and the resin was washed twice with ethanol (the resin was vacuum dried after washing). The liquid phases were combined and concentrated under reduced pressure to give 453 mg of palmitic acid monoethanolamide in 96.6% yield and >99.5% purity (HPLC detection).