2,5-Dihydro-4-methyl-2,5-dioxo-3-furanpropanoic Acid

13192-04-6

3699-66-9

487-66-1

Example 4: Synthesis of Masking Agent A - Preparation of 2-propanoic acid-3-methylmaleic anhydride (carboxydimethylmaleic anhydride or CDM) precursor 1. Suspend sodium hydride (0.58 g, 25 mmol) in 50 mL of anhydrous tetrahydrofuran to which triethyl 2-phosphonopropyl ester (7.1 g, 30 mmol) was added. After the hydrogen release stopped, dimethyl α-ketoglutarate (15 g, 20 mmol) dissolved in 10 mL of anhydrous tetrahydrofuran was added and the reaction mixture was stirred for 30 minutes. 2. Upon completion of the reaction, 10 mL of water was added and the tetrahydrofuran was removed by rotary evaporation. The resulting solid-water mixture was extracted with ether (3 x 50 mL). The ether layers were combined, dried with magnesium sulfate and concentrated to give a light yellow oil. 3. The above oil was purified by silica gel column chromatography with the eluent of ether:hexane (2:1) to give 4 g of pure triglyceride (82% yield). 4. The resulting triglyceride was dissolved in 50 mL of a solvent mixture of water and ethanol (ratio 50:150) and potassium hydroxide (4.5 g, 5 eq.) was added. The reaction mixture was heated to reflux for 1 hour. 5. Upon completion of the reaction, the ethanol was removed by rotary evaporation and the solution was acidified with hydrochloric acid to pH 2. Subsequently, the aqueous solution was extracted with ethyl acetate (200 mL), the organic layer was separated, dried with magnesium sulfate and concentrated to give a white solid. 6. Finally, the white solid was recrystallized by dichloromethane and hexane to give 2 g of 2-propanoic acid-3-methylmaleic anhydride (80% yield).