Acetic Acid → Methyl 4-bromo-8-oxo-5,6,7,8-tetrahydroisoquinoline-7-carboxylate

Participants

Reaction Steps

Ethyl 5-bromo-4-methylnicotinate (7.04 g, 28.8 mmol) in THF (28.8 mL) was added over a period of 20 min to a solution of LDA (31.7 mmol) [generated from N,N-diisopropylamine (4.52 mL, 31.7 mmol) and n-butyllithium (19.8 mL, 31.7 mmol, 1.6M in hexane) in THF (144 mL)] at −78° C. The resulting dark red solution was stirred for 20 min, then methyl acrylate (6.5 mL, 72.1 mmol) in THF (28.8 mL) was added over 15 min. The reaction was stirred an additional 1.5 h, then aq. 10% AcOH (57.8 mL, 101 mmol) was added (pH 4-5) and the reaction was allowed to warm to room temperature. After evaporation, the residue was partitioned between aq. sat. NaHCO3 and EtOAc and extracted with EtOAc (3×). The combined organic layers were dried (Na2SO4) and concentrated to afford the title compound (7.80 g, 95% in 70% purity with 30% starting material) as brown solid. MS: 280.0 (M+H+, 1Br).

Provenance & Evidence