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

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+, 1 Br).

1. stirringThe reaction was stirred an additional 1.5 h
2. customAfter evaporation
3. customthe residue was partitioned between aq. sat. NaHCO3 and EtOAc
4. extractionextracted with EtOAc (3×)
5. dry with materialThe combined organic layers were dried (Na2SO4)
6. concentrationconcentrated

ORD record

ord-4d30fe4a37ec44979c91fd248e123842

Source dataset

uspto-grants-2015_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09187429B2