Triphenylphosphine → 6-Isoquinolinecarboxylic acid, methyl ester

Participants

Reaction Conditions

Reaction Steps

To a solution of 6-bromoisoquinoline (10 g, 48 mmol), purchased from Gateway Chemical Technology, Inc., in 200 mL of 1:1 DMF:MeOH was added sodium acetate (5.0 g, 61 mmol), triphenylphosphine (3.8 g, 14 mmol), and palladium(II) acetate (2.8 g, 12 mmol). The vessel was charged with 300 kPa of carbon monoxide. The vessel was then purged. This charging purging sequence was repeated three times, then the vessel was charged with 300 kPa of CO and heated to 100° C. After 15 hours, the reaction was judged to be complete by LC/MS. The reaction was filtered through Celite (eluting with EtAOc) and the resulting mixture was concentrated under reduced pressure. The residue was taken up in 250 mL of EtOAc and washed three times with water and once with brine. The mixture was then dried over MgSO4, filtered, and concentrated under reduced pressure. Flash chromatography on silica gel (10% to 35% EtOAc/hexanes) afforded methyl isoquinoline-6-carboxylate as a white powder (7.0 g, 78% yield): LCMS (API ES) m/z 188 [M+1+].

Provenance & Evidence