tert-Butylacetic acid → Neotame

Participants

Reaction Steps

Aspartame (11.76 g), tertbutylacetic acid (4.64 g) and methanol (100 ml) were charged to a hydrogenation vessel. 3,3-Dimethylbutyraldehyde (4.0 g) was added. The vessel was pressure purged with nitrogen (4×), and 0.48 g of 4% palladium on carbon (containing 50% water) was added. After pressure purging the reactor with nitrogen (4×), followed by hydrogen (4×), the mixture was hydrogenated at 50 psig for 12 hours at room temperature. After completion of the reaction, the vessel was pressure purged with nitrogen (4×). The catalyst was removed from the reaction mixture by filtration through powdered cellulose. Methanol (50 ml) was used to rinse the reaction vessel and the filter cake. The filtrate and wash were combined, and methanol was evaporated under reduced pressure. The solution was reduced to 75 ml total volume, and 75 g of deionized water was added. The remaining methanol was evaporated from the solution under reduced pressure. The resulting solution was stirred at room temperature for 12 hours. Hexane (75 ml) was added, and the solution was stirred for 3 hours at room temperature. The crystallized solid was isolated by filtration and washed with 50 ml deionized water and 50 ml of hexane. The wet product was dried in air to give 8.1 g of neotame (>98% by HPLC).

Provenance & Evidence