Sodium Carbonate → 8-(5-Ethoxycarbonylmethyl-2-methoxy-phenyl)-5-fluoro-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester

Participants

Reaction Conditions

Reaction Steps

To a mixture under N2 of 8-bromo-5-fluoro-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester (1.24 g, 3.75 mmol, 1.00 eq.), [4-methoxy-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-acetic acid ethyl ester (1.69 g, 3.75 mmol, 1.00 eq.) and sodium carbonate (1.59 g, 15.00 mmol, 4.00 eq.) in toluene/MeOH/water 20:4:1 (75 mL), tetrakis(triphenylphosphine) palladium (0) (217 mg, 0.19 mmol, 0.05 eq.) was added and the mixture was stirred under reflux at 100° C. for 70 hours. The mixture was allowed to cool to r.t. and concentrated in vacuo. The residue was partitioned between AcOEt (150 mL) and water (150 mL). The layers were separated. The org. phase was washed with sat. aq. NaCl soln. (1×75 mL), dried over MgSO4 and filtered through Celite. The filtrate was concentrated in vacuo. The residue was purified by flashmaster (column: 100 g, flow: 45 mL/min, 30 fractions of 40 mL, Heptane+10% AcOEt to Heptane+25% AcOEt) to yield the desired ester as a pale yellow oil.

Provenance & Evidence