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103606-72-0

Example 1: Preparation of tert-butoxy-[4-(4-methoxy-3,5-dimethylphenyl)-2-methyl-1-oxo-1,2-dihydroisoquinolin-3-yl]-acetic acid Step A: Synthesis of methyl 2-(3-hydroxyprop-1-ynyl)-benzoate Methyl 2-iodobenzoate (88.0 g, 335.9 mmol), 2-propyn-1-ol (28.3 g, 503.8 mmol), copper iodide (1.2 g, 6.7 mmol), Pd(PPh3)2Cl2 (7.0 g, 10.0 mmol), and triethylamine (68.0 g, 671.8 mmol) were suspended in acetonitrile (1 L). The solution was bubbled with N2 for 20 min to deoxidize. Subsequently, the reaction mixture was stirred at reflux for 3 h under N2 protection. After completion of the reaction, the mixture was filtered and the filtrate was concentrated to dryness. The residue was purified by column chromatography to afford the target product methyl 2-(3-hydroxyprop-1-ynyl)-benzoate (58.8 g, 92.0% yield). 1H NMR (400 MHz, d6-DMSO): δ 2.48 (t, J = 6.2 Hz, 1H), 3.88 (s, 3H), 4.52 (d, J = 5.6 Hz, 2H), 7.32 (t, J = 7.6 Hz, 1H), 7.41 (t, J = 7.6 Hz, 1H), 7.51 (d, J = 7.6 Hz, 1H), 7.90 (d, J = 7.6 Hz, 1H), 7.90 (d, J = 7.6 Hz, 1H). 7.90 (d, J = 7.2 Hz, 1H).