Reaction #2049598
ord-50dd64eec9da4c199a6e4a8f32450fcb
Reaction equation
Reactants
Reagents
Conditions
Procedure
A mixture of palladium acetate (21 mg, 0.095 mmol), 4,5-bis-diphenylphosphanyl-9,9-dimethyl-9H-xanthene (=Xantphos, 55 mg, 0.095 mmol), sodium carbonate (303 mg, 2.86 mmol), 4-bromo-8-fluoro-3-methyl-2-oxazol-2-ylmethyl-2H-isoquinolin-1-one (321 mg, 0.952 mmol), and benzyl alcohol (0.297 mL, 2.87 mmol) in toluene (3 mL, 30 mmol) was stirred under an atmosphere of carbon monoxide (P=3 bar) at 110° C. overnight. LC/MS indicated the formation of the title product and its benzyl ester (8-fluoro-3-methyl-2-oxazol-2-ylmethyl-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid benzyl ester) in ca. 1:1 ratio. The reaction mixture was dissolved in 5 ml of ethanol, filtered through a short plug of celite and evaporated. It was partitioned between ethyl acetate (50 ml) and 0.5M aq. NaOH (2×25 ml). The combined aqueous solution was acidified with conc. aq. HCl, extracted with ethyl acetate (40 ml), the organic phase was washed with brine, dried (MgSO4) and evaporated to give 105 mg of the title product, yield 36.5%. LC-MS (m/z) 303.3 (MH+), tR=0.57.