General procedure for the synthesis of tert-butyl 6-(hydroxymethyl)-3,4-dihydroisoquinoline-2(1H)-carboxylate from 2-(tert-butoxycarbonyl)-1,2,3,4-tetrahydroisoquinoline-6-carboxylic acid: In Example 16, tert-butyl 6-bromomethyl-3,4-dihydro-1H-isoquinoline-2- carboxylate (D-1 ), the intermediate 6-bromomethyl-3,4-dihydro-1H-isoquinoline-2-carboxylic acid, was prepared as follows: firstly, under nitrogen protection, the Borane-THF complex (99.17 mL, 99.17 mmol) was slowly added to a solution of 2-(tert-butoxycarbonyl)-1,2,3,4-tetrahydroisoquinoline-6-carboxylic acid (12.50 g, 45.08 mmol) in anhydrous THF (125.0 mL) via a syringe, and the reaction lasted for 16 h at 25 °C. Subsequently, water (10.0 mL) was slowly added followed by 2.0 M Na2CO3 solution (15.0 mL). The mixture was stirred for 15 min and then diluted with EtOAc to separate the organic layer. The organic layer was washed with 1 M HCl, dried over MgSO4 and concentrated under reduced pressure to give an oil. The oily substance was purified by silica gel chromatography to give the intermediate D-1-1 (11.8 g, 99.3% yield) as a white solid. Next, D-1-1 (9.50 g, 36.1 mmol) and N,N-diisopropylethylamine (9.43 mL, 54.1 mmol) were dissolved in dichloromethane (200.0 mL), triphenylphosphine dibromide (23.79 g, 54.11 mmol) was added, and the reaction was stirred for 1 hr and concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography to afford the target product D-1 (8.74 g, 74% yield) as a white solid.
