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

Participants

Reaction Conditions

Reaction Steps

Dimethyl 2-(cyanomethyl)-5-(propan-2-yloxy)benzene-1,3-dicarboxylate (Cpd D, 1.04 g, 3.57 mmol) and cobalt (II) chloride hexahydrate (2.56 g, 10.7 mmol) were dissolved in MeOH (60 mL) and cooled in an ice bath. NaBH4 (853 mg, 21.4 mmol) was added portionwise and the reaction mixture was stirred at 0° C. for 0.5 hours. To the reaction mixture was added NH4Cl (sat., aq., 25 mL), H2O (25 mL), and EtOAc (50 mL). The solution was allowed to sit at room temperature overnight. The residual solids were filtered and the aqueous layer was extracted with EtOAc (3×50 mL). The combined organic layers were washed with brine (1×50 mL), dried over sodium sulfate, concentrated under vacuum, and purified by column chromatography (0-60%, EtOAc/heptanes) to afford methyl 1-oxo-7-(propan-2-yloxy)-1,2,3,4-tetrahydroisoquinoline-5-carboxylate (Cpd E, 644 mg, 69% yield) as a white solid. 1H NMR (400 MHz, chloroform-d) δ 1.35 (s, 3H) 1.36 (s, 3H) 3.35 (t, J=6.57 Hz, 2H) 3.52 (td, J=6.57, 3.03 Hz, 2H) 3.91 (s, 3H) 4.61-4.72 (m, 1H) 5.91 (br. s., 1H) 7.62 (d, J=3.03 Hz, 1H) 7.83 (d, J=3.03 Hz, 1H); MS 264.1 [M+H].

Provenance & Evidence