Synthesis
7-Nitro-1,2,3,4-tetrahydroisoquinoline hydrochloride was synthesized as follows: 1,2,3,4-tetrahydroisoquinoline (13.3 g, 0.1 mol) was dissolved in concentrated sulfuric acid (50 mL) and cooled to 0-5°C. At this temperature, potassium nitrate (11.12 g, 1.1 mol) was added in batches to ensure that the temperature of the reaction did not exceed 5°C. After addition, the reaction was allowed to proceed. After addition, the mixture was stirred at room temperature overnight. After completion of the reaction, the mixture was slowly poured into ice water. The pH was adjusted to alkaline with ammonium hydroxide solution and subsequently extracted with dichloromethane (CH2Cl2). The organic layers were combined, dried with anhydrous sodium sulfate, filtered and concentrated to dryness under reduced pressure. The crude product was dissolved in ethanol (100 mL) and 2.8 M ethanol solution of hydrogen chloride (40 mL) was added. The precipitated solid was collected by filtration and recrystallized from methanol to give the white solid product 7-nitro-1,2,3,4-tetrahydroisoquinoline hydrochloride (10.30 g, 48% yield). The melting point of the product was 268-270°C. IR (KBr, cm-1): 2944, 2764, 1589, 1523, 1429, 1345, 1090. 1H NMR (300 MHz, DMSO-d6) δ ppm: 3.13 (t, J = 6.15 Hz, 2H), 3.35 (t, J = 6.22 Hz, 2H), 4.35 (s, 2H). 4.35 (s, 2H), 7.50 (d, J = 8.49 Hz, 1H), 8.08 (dd, J = 8.49, 2.49 Hz, 1H), 8.19 (d, J = 2.34 Hz, 1H), 9.96 (s, 2H).
References
[1] Patent: US2010/234340, 2010, A1. Location in patent: Page/Page column 21
[2] Patent: US2006/40978, 2006, A1. Location in patent: Page/Page column 9
[3] Chemistry - A European Journal, 2009, vol. 15, # 4, p. 885 - 900
[4] Patent: EP3363803, 2018, A1. Location in patent: Paragraph 0153
[5] Patent: EP3401315, 2018, A1. Location in patent: Paragraph 0148; 0149
