A slurry was formed in dichloromethane (DCM, 1 L) using 2-chloro-5,6,7,8-tetrahydro-1,6-naphthyridine hydrochloride (106.1 g, 517 mmol) and N,N-diisopropylethylamine (80 g, 108 mL, 621 mmol, 1.2 equiv.) as starting materials. A solution of di-tert-butyl dicarbonate (119 g, 543 mmol, 1.05 eq.) in DCM (100 mL) was slowly added through the addition funnel over a period of 1 hour. The reaction mixture was gradually converted to a clarified solution, followed by continued stirring at room temperature for 1 h. The reaction progress was monitored by LCMS. Upon completion of the reaction, the mixture was concentrated. The concentrated residue was dissolved in ethyl acetate (EtOAc, 1 L), washed sequentially with water (3 x 300 mL) and brine (300 mL), and the organic phase was dried with anhydrous magnesium sulfate (MgSO4). The solvent was removed by evaporation under reduced pressure to afford 2-chloro-7,8-dihydro-1,6-naphthyridine-6(5H)-carboxylic acid 1,1-dimethylethyl ester as an off-white solid (139 g, yield: 100%). The product was characterized by 1H NMR (400 MHz, CDCl3) and LCMS: 1H NMR δ 1.49 (9H, s), 2.97 (2H, t, J = 5.9 Hz), 3.73 (2H, t, J = 6.0 Hz), 4.57 (2H, s), 7.17 (1H, d, J = 8.0 Hz), 7.38 (1H, d, J = 8.0 Hz) ppm; LCMS m/z: 269 (M + 1).
