N-Boc-glycine methyl ester → Methyl 2-Boc-8-bromo-4-oxo-1,2,3,4-tetrahydroisoquinoline-3-carboxylate

Participants

Reaction Steps

To a flask containing methyl 2-((tert-butoxycarbonyl)amino)acetate (4.18 g, 22.09 mmol) in anhydrous DMF (50 ml) was added KOtBu (3.99 g, 35.6 mmol) then after 1 min at room temperature added methyl 3-bromo-2-(bromomethyl)benzoate (4.97 g, 16.14 mmol) as a solid in 1 portion. The reaction mixture was then capped (not under N2) & stirred at room temperature for 3 hours. Followed by LC/MS. The reaction mixture was quenched/diluted with sat'd NaHCO3, then suspended in EtOAc, washed with saturated NaHCO3, then H2O, then brine; organics dried over Na2SO4, filtered & concentrated. Purification by silica gel chromatography (0-20% EtOAc/Hex; 220 g ISCO); desired fractions concentrated to yield 2-tert-butyl 3-methyl 8-bromo-4-oxo-3,4-dihydroisoquinoline-2,3 (1H)-dicarboxylate (24-1).

Provenance & Evidence