Synthesis
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).
References
[1] Patent: WO2012/102985, 2012, A1. Location in patent: Page/Page column 94
[2] Doklady Chemistry, 1985, vol. 283, p. 212 - 214
[3] Dokl. Akad. Nauk SSSR Ser. Khim., 1985, vol. 283, # 3, p. 630 - 633
[4] Beilstein Journal of Organic Chemistry, 2014, vol. 10, p. 996 - 1005
[5] Organic Letters, 2018, vol. 20, # 10, p. 3034 - 3038
