Abstract. Phth-AIB-OH was prepared in 65% yield by refluxing AIB with one equivalent of phthalic anhydride and a catalytic amount of Et3N in toluene for 23 hours.
Procedure. Phthalic anhydride (7.2 g, 48.6 mmol) was combined with 2-amino isobutyric acid (AIB, 5.09 g, 49.4 mmol) and triethylamine (0.7 mL, 5 mmol) in toluene (150 mL) in a 500 mL round-bottom flask equipped with a Dean-Stark trap and magnetic stir bar. The mixture was refluxed for 23 hours and monitored by TLC (silica gel, 2:1 hexane:ethyl acetate, UV detection). TLC after 23 hours showed product and phthalic anhydride.
The cooled reaction mixture contained a white solid. Saturated aqueous NaHCO3
(50 mL) was added to the reaction mixture, and the mixture was stirred until
all solids had dissolved. The layers were separated, and the aqueous layer was
washed with diethyl ether (25 mL). The resulting mixture was acidified (pH <
2) with 3M HCl (approximately 16 mL), producing a white foamy precipitate. The
product was recovered by vacuum filtration, washed with a small volume of water,
air-dried briefly on the filter, and then dried under vacuum and stored in a
dessicator. The product was obtained
as a white solid: 7.421 g (65%); mp 154-155 °C; 1H NMR
(DMSO-d6, 400 MHz) ppm: 1.68 (s, CH3), 7.81 (m, Ar-H) (KRR 5).