Synthesis of Acetonide-Protected Bis-MPA

In a 250 mL round bottom flask equipped with a magnetic stirrer, 2,2-bis(hydroxymethyl)propionic acid (bis-MPA, 32.00 g, 0.239 mol), acetone (120.0 mL), and 2,2-dimethoxypropane (30.0 mL, 0.244 mol) were sequentially added and stirred under argon at room temperature. Then, the solution of p-toluenesulfonic acid monohydrate (PTSA.H₂O, 0.40 g, 2.11 × 10⁻³ mol) in acetone (5.0 mL) was injected into the reaction flask. After 90 min, 2,2-dimethoxypropane (20.0 mL, 0.163 mol) was added and stirred to obtain a homogenous solution. The reaction was continuously stirred at room temperature for 180 min. To stop the reaction, the solution of saturated sodium bicarbonate (NaHCO₃, 30.0 mL) was added and stirred for 2 min. The mixture was concentrated before being extracted with diethyl ether (2 × 80.0 mL). The organic phase was then washed with brine solution (2 × 40.0 mL), dried with sodium sulfate (Na₂SO₄), filtered, and concentrated under reduced pressure at 40 °C to obtain the white solid (33.82 g). Yield: 81.3%.
¹H NMR (400 MHz, acetone D₆) δ (ppm): 4.15 (-OCH₂-, d, J = 11.7 Hz), 3.65 (-OCH₂-, d, J = 11.7 Hz), 1.39 and 1.33 (-CH₃ of acetonide), and 1.19 (-CH₃, s). ¹³C NMR (101 MHz, acetone D₆) δ (ppm): 174.80 (-COOH), 97.50 (-OC(CH₃)₂O-), 65.58 (-OCH₂-), 41.07 (C(CH₃)COOH), 23.76 and 22.52 (-CH₃ of acetonide), and 18.08 (-CH₃).