2-O-tert-butyl 1-O-methyl 5-bromo-3,4-dihydro-1H-isoquinoline-1,2-dicarboxylate

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of Intermediate 4B (5.0 g, 13.50 mmol) in THF (60 mL)/MeOH (60 mL) was added 1N NaOH (40.5 ml, 40.5 mmol). After 24 h, the reaction mixture was concentrated and the remaining aqueous layer cooled to 0° C. and the pH was adjusted to 5 using 1.0N HCl solution. The solution was extracted with EtOAc (3×75 mL). The combined organic extracts were washed with brine, dried (MgSO4), filtered, and concentrated to give 4.75 g (99%) of Intermediate 4 as a white solid. 1H NMR (500 MHz, DMSO-d6) δ 7.55 (dd, J=17.2, 7.8 Hz, 2H), 7.20 (t, J=7.8 Hz, 1H), 5.49-5.32 (m, 1H), 3.86-3.73 (m, 1H), 3.59-3.48 (m, 1H), 2.92-2.74 (m, 2H), 1.42 (d, J=12.9 Hz, 9H) ppm. MS (ESI) m/z: 255.9 (M+H-tBoc)+. the reaction mixture was concentrated The solution was extracted with EtOAc (3×75 mL) The combined organic extracts were washed with brine dried (MgSO4) filtered concentrated

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of Intermediate 4B (5.0 g, 13.50 mmol) in THF (60 mL)/MeOH (60 mL) was added 1N NaOH (40.5 ml, 40.5 mmol). After 24 h, the reaction mixture was concentrated and the remaining aqueous layer cooled to 0° C. and the pH was adjusted to 5 using 1.0N HCl solution. The solution was extracted with EtOAc (3×75 mL). The combined organic extracts were washed with brine, dried (MgSO4), filtered, and concentrated to give 4.75 g (99%) of Intermediate 4 as a white solid. 1H NMR (500 MHz, DMSO-d6) δ: 7.55 (dd, J=17.2, 7.8 Hz, 2H), 7.20 (t, J=7.8 Hz, 1H), 5.49-5.32 (m, 1H), 3.86-3.73 (m, 1H), 3.59-3.48 (m, 1H), 2.92-2.74 (m, 2H), 1.42 (d, J=12.9 Hz, 9H) ppm. the reaction mixture was concentrated The solution was extracted with EtOAc (3×75 mL) The combined organic extracts were washed with brine dried (MgSO4) filtered concentrated

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of Intermediate 4B (5.0 g, 13.50 mmol) in THF (60 mL)/MeOH (60 mL) was added 1N NaOH (40.5 ml, 40.5 mmol). After 24 h, the reaction mixture was concentrated and the remaining aqueous layer cooled to 0° C. and the pH was adjusted to 5 using 1.0N HCl solution. The solution was extracted with EtOAc (3×75 mL). The combined organic extracts were washed with brine, dried (MgSO4), filtered, and concentrated to give 4.75 g (99%) of Intermediate 4 as a white solid. 1H NMR (500 MHz, DMSO-d6) δ 7.55 (dd, J=17.2, 7.8 Hz, 2H), 7.20 (t, J=7.8 Hz, 1H), 5.49-5.32 (m, 1H), 3.86-3.73 (m, 1H), 3.59-3.48 (m, 1H), 2.92-2.74 (m, 2H), 1.42 (d, J=12.9 Hz, 9H) ppm. MS (ESI) m/z: 255.9 (M+H-tBoc)+. the reaction mixture was concentrated The solution was extracted with EtOAc (3×75 mL) The combined organic extracts were washed with brine dried (MgSO4) filtered concentrated