Uses
N-Boc-1,2,3,4-Tetrahydroisoquinoline-6-carboxylic Acid is the starting material used to prepare benzazole derivatives as β-secretase inhibitors useful in treatment and prevention of diseases.
Synthesis
Step 2: Synthesis of 2-(tert-butoxycarbonyl)-1,2,3,4-tetrahydroisoquinoline-6-carboxylic acid; To a mixture of methanol/tetrahydrofuran (1:1, 6 mL) of the crude urethane obtained from Step 1 was added 1N sodium hydroxide solution (1.97 mL, 1.97 mmol). The reaction mixture was heated to 70 °C and maintained for 1 hour. After the reaction was completed, the mixture was cooled and methanol was removed by rotary evaporator. The remaining aqueous solution was acidified to pH 4 with 1 N hydrochloric acid.The resulting precipitate was collected by vacuum filtration and dried to give the target product (0.34 g, 93% yield), which could be used in subsequent reactions without further purification. Mass spectrum (electrospray positive ion mode) m/e 222.0 [M-tBu]+.
References
[1] Journal of Medicinal Chemistry, 2004, vol. 47, # 21, p. 5167 - 5182
[2] Patent: WO2009/49154, 2009, A1. Location in patent: Page/Page column 40
[3] Patent: EP3192791, 2017, A1. Location in patent: Paragraph 0596
[4] European Journal of Medicinal Chemistry, 2019, p. 317 - 333
[5] Patent: WO2006/114313, 2006, A1. Location in patent: Page/Page column 159
