Synthesis
The general procedure for the synthesis of (R)-2-(4-methylphenylsulfonylamino)-3-phenylpropanoic acid from D-phenylalanine and p-toluenesulfonyl chloride was as follows: at room temperature, D-phenylalanine (1 g, 6 mmol) was suspended in 25 mL of water, followed by the addition of NaOH (0.72 g, 18 mmol) and p-toluenesulfonyl chloride (1.37 g, 7.2 mmol). The reaction mixture was stirred at 60 °C for 6 hours. After completion of the reaction, the products were separated by acid-base washing method. This was done by adding 3M HCl and EtOAc to the reaction mixture and adjusting the pH to 1, which resulted in the protonation and transfer of D-phenylalanine to the aqueous phase, while the product was transferred to the organic phase. Subsequently, the pH was adjusted to 11-12 by adding 2M NaOH aqueous solution to deprotonate the product and transfer it back to the aqueous phase. Finally, the pH was adjusted again by adding 3M HCl to protonate the product and transfer it to the organic phase. The organic phase was washed with brine, dried with MgSO4, and the target product (1.80 g, 95% yield) was obtained by evaporating the solvent.
References
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[5] Chemische Berichte, 1915, vol. 48, p. 374
