L-Alanine methyl ester hydrochloride

Chemical Properties

Uses

reaction suitability

Synthesis

67-56-1

56-41-7

2491-20-5

The general procedure for the synthesis of (S)-alanine methyl ester hydrochloride (1a) from methanol and L-alanine was as follows: 15 mL of anhydrous methanol was first added to a round-bottomed flask according to the literature (Xing et al., 2012). At -15 °C, 2.16 mL of SOCl2 (0.03 mol) was slowly added dropwise to methanol and the reaction was maintained at 0 °C for 1 hour. Another round bottom flask was taken and 14 mL of anhydrous methanol and 1.4 mL (0.019 mol) of SOCl2 was added followed by 1.118 g of L-alanine and heated to reflux for 1.5 hours. Upon completion of the reaction, the solution was concentrated under reduced pressure, and the pre-prepared SOCl2 solution was poured into the reaction flask and refluxing was continued for 1.5 h to give product 1a (100% yield). Since the hydrochloric acid generated by the reaction was not favorable for the subsequent steps, NaHCO3 was added to the reaction flask at the end of reflux to neutralize the acidity until no bubbles were generated. Finally, the solution was concentrated to obtain 1b (100% yield). Fusaric acid (4) was dissolved with 1b in 15 mL of dichloromethane in a round-bottomed flask with homogeneous stirring, followed by the addition of excess catalysts dicyclohexylcarbodiimide (DCC) and 4-dimethylaminopyridine (DMAP), and refluxed for 24 hours. Upon completion of the reaction, the reaction solution was concentrated under reduced pressure and purified by preparative HPLC (25-45% CH3CN/H2O, 20 min) to afford the product 1c (52% yield).

References