Chlorosuccinimide → Methyl 8-chloro-1-oxo-7-(propan-2-yloxy)-1,2,3,4-tetrahydroisoquinoline-5-carboxylate

Participants

Reaction Conditions

Reaction Steps

To a solution of methyl 1-oxo-7-(propan-2-yloxy)-1,2,3,4-tetrahydroisoquinoline-5-carboxylate (Cpd E, 400 mg, 1.52 mmol) in AcOH (5 mL) was added NCS (416 mg, 3.04 mmol). The reaction mixture was stirred at 100° C. overnight. The reaction mixture was concentrated under vacuum and the residue was diluted with H2O and NaHCO3 (sat., aq.). The aqueous layer was extracted with EtOAc and the organic layer purified by column chromatography (50% EtOAc/heptanes) to give the title compound (Cpd F, 180 mg, 40%) as a white solid. 1H NMR (400 MHz, chloroform-d) δ 1.40 (s, 3H) 1.42 (s, 3H) 3.27-3.36 (m, 2H) 3.37-3.47 (m, 2H) 3.88-3.95 (m, 3H) 4.62 (dt, J=12.07, 6.13 Hz, 1H) 6.06 (br. s., 1H) 7.61 (s, 1H); MS 298.0 [M+H].

Provenance & Evidence