Phenylboronic Acid → (S)-2-(7-phenyl-1-oxo-1H-isoquinolin-2-yl)-butyric acid

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To a solution of (S)-2-(7-chloro-1-oxo-1H-isoquinolin-2-yl)-butyric acid (prepared as described in methods A-E) (200 mg) and phenyl boronic acid (276 mg) in THF (2 ml) was added palladium (II) acetate (1.7 mg), 2-(di-tert-butylphosphino)biphenyl (4.5 mg) and potassium fluoride (262 mg). The resulting mixture was heated at reflux for 18 hours, then cooled and diluted with 1M HCl (5 ml) and ethyl acetate (15 ml). The organic phase was separated and the aqueous extracted with ethyl acetate (2×15 ml). The combined organics were dried (magnesium sulfate), filtered and concentrated. The residue was purified through a plug of silica gel, then further purified by radial chromatography eluting with 1% acetic acid in ethyl acetate. This gave the subtitled product as a brown solid (153 mg, 66%). 1H NMR (400 MHz, CDCl3) δ 1.00 (3H, t), 2.15 (1H, m), 2.40 (1H, m), 5.37 (1H, m), 6.70 (1H, d), 7.15 (1H, d), 7.45 (1H, m), 7.55 (2H, m), 7.68 (1H, m), 7.75 (2H, m), 7.99 (1H, d), 8.70 (1H, s) ppm.

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