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. Sodium bicarbonate (47.4 g, 564 mmol) and di-tert-butyl dicarbonate (67.7 g, 310 mmol) were subsequently 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 and the residue was dissolved in water (2000 mL). A 30% w/v aqueous solution of sodium bisulfate monohydrate (300 mL) was added and extracted with chloroform (3 x 1000 mL). The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, and 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.Results of LCMS analysis: retention time 3.64 min; mass spectrometry data m/z 178.1 [M-Boc + 2H]+ ; m/ z 276.1 [M-H]-.
