Synthesis
Synthesis of Intermediate 8a: Methyl 2-(4-aminophenyl)acetate
4-Aminophenylacetic acid (10.0 g, 66.6 mmol) was dissolved in methanol (350 mL), stirred and concentrated. Concentrated sulfuric acid (3.88 mL, 72.77 mmol) was added slowly and dropwise. The reaction mixture was stirred at 50 °C overnight and subsequently cooled to room temperature and concentrated under vacuum. The concentrated mixture was diluted with water, neutralized with sodium carbonate (Na2CO3) until the solid precipitated, and then extracted with dichloromethane (DCM). The organic layer was dried with anhydrous sodium sulfate (Na2SO4), filtered and concentrated to give methyl 2-(4-aminophenyl)acetate (9.75 g, 59.02 mmol, 89% yield).
Method 2: RT: 0.60 min, m/z 165.9 [M + H]+.
References
[1] Patent: US2014/303218, 2014, A1. Location in patent: Paragraph 0088-0089
[2] Dalton Transactions, 2018, vol. 47, # 15, p. 5259 - 5268
[3] Patent: WO2016/51193, 2016, A1. Location in patent: Paragraph 00249; 00250; 00251
[4] Bioorganic and Medicinal Chemistry Letters, 2009, vol. 19, # 6, p. 1784 - 1789
[5] Journal of Medicinal Chemistry, 1997, vol. 40, # 7, p. 1049 - 1062
