反应详情

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.

1. customby degassed anhydrous MeOH (6 mL) & DMSO (3 mL)
2. customThis mixture was then degassed
3. customby bubbling N2 through with a vent needle
4. customthe reaction was purged 3× (vacuum/CO)
5. temperaturethe reaction mixture (clear tan, became darker with heat)
6. temperaturewas heated to 80 C
7. stirringwhile stirring in a hot oil bath in the hood under an atmosphere of CO
8. waitAfter 22 hours
9. washwashed with saturated NaHCO3
10. dry with materialorganics dried over Na2SO4
11. filtrationfiltered
12. concentrationconcentrated
13. customPurification by silica gel chromatography (0-40% EtOAc/Hex; 40 g ISCO)
14. concentrationdesired fractions concentrated