General procedure for the synthesis of (S)-(+)-N-benzyloxycarbonyl-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid from (S)-(-)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid and benzyl chloroformate: to an aqueous solution of 1 M NaOH (3.20 g, 80.0 mmol, dissolved in 80 mL of H2O) was added slowly at room temperature (S)-1 ,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (5.00 g, 28.2 mmol) and dioxane until the suspension was completely dissolved. Subsequently, benzyl chloroformate (6.25 g, 5.59 mL, 36.7 mmol) was added slowly and dropwise over 30 min at 0 °C. The reaction mixture was stirred at room temperature for 16 hours. Dioxane was removed by evaporation and the reaction mixture was acidified with 1 M HCl to pH 2 at 0 °C. The aqueous layer was extracted with EtOAc and the combined organic layers were dried over Na2SO4, filtered and evaporated in vacuo to afford the target product, (S)-(+)-N-benzyloxycarbonyl-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (8.68 g, 27.9 mmol, 99% yield), as a white foamy solid without further purification. The product was characterized by 1H-NMR, 13C-NMR, MS and LC-MS to confirm its structure and purity.
