Triethylamine → 2-tert-Butyl 8-methyl 4-fluoro-3,4-dihydroisoquinoline-2,8(1H)-dicarboxylate

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Reaction Steps

To a flask containing tert-butyl 8-bromo-4-fluoro-3,4-dihydroisoquinoline-2(1H)-carboxylate (24-5) (316 mg, 0.957 mmol) was added TRIETHYLAMINE (0.6 mL, 4.30 mmol), followed by degassed anhydrous MeOH (6 mL) & DMSO (3 mL). This mixture was then degassed by bubbling N2 through with a vent needle while stirring for ˜5 minutes. Then added PdOAc2 (57 mg, 0.254 mmol) & DPPP (83 mg, 0.201 mmol) as solids in 1 portion. A balloon containing CARBON MONOXIDE (536 mg, 19.14 mmol) was then attached and the reaction was purged 3× (vacuum/CO), then the reaction mixture (clear tan, became darker with heat) was heated to 80 C while stirring in a hot oil bath in the hood under an atmosphere of CO. Followed by LC/MS. After 22 hours, the reaction mixture was suspended in EtOAc, washed with saturated NaHCO3, then H2O, then brine; organics dried over Na2SO4, filtered & concentrated. Purification by silica gel chromatography (0-40% EtOAc/Hex; 40 g ISCO); desired fractions concentrated to yield 2-tert-butyl 8-methyl 4-fluoro-3,4-dihydroisoquinoline-2,8(1H)-dicarboxylate (24-6). HRMS [M+H]: calculated; 310.1449, observed; 310.1439.

Provenance & Evidence