The general procedure for the synthesis of (R)-2-(tert-butoxycarbonyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid from di-tert-butyl dicarbonate and (S)-(-)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid was as follows: (S)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (50.0 g, 282 mmol) was suspended in 1,4-dioxane ( 1000 mL) and water (500 mL) in a solvent mixture with vigorous stirring. Subsequently, sodium bicarbonate (47.4 g, 564 mmol) and di-tert-butyl dicarbonate (67.7 g, 310 mmol) were added and the reaction mixture was stirred continuously at room temperature for 6 days. After completion of the reaction, the mixture was concentrated under reduced pressure to remove the solvent. The concentrated residue was dissolved in water (2000 mL) and acidified by adding 30% w/v aqueous sodium bisulfate monohydrate (300 mL). The acidified aqueous phase was extracted with chloroform (3 x 1000 mL) and the organic phases were combined. The organic phases were sequentially washed with saturated saline, dried over anhydrous sodium sulfate, and subsequently concentrated under reduced pressure to afford the target product (R)-2-(tert-butoxycarbonyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (90.0 g, quantitative yield) as a thick slurry. The product was confirmed by LCMS analysis: retention time (RT) 3.64 min; mass spectral data: m/z 178.1 [M-Boc + 2H]+; m/z 276.1 [M-H]-.
