Synthesis
The general procedure for the synthesis of (S)-1-(tert-butoxycarbonyl)-2-acridinemethanol from 1-Boc-L-acridine-2-carboxylic acid was as follows:Example 16 Synthesis of tert-butyl (S)-2-(hydroxymethyl)azetidine-1-carboxylate (14). To a solution of 13 (0.94 g, 4.7 mmol) in tetrahydrofuran (THF, 10 mL) was slowly added a THF solution (21.0 mL) of 1 M borane (BH3) at 0 °C. The reaction mixture was stirred at room temperature for 2 days. Subsequently, the reaction was quenched by the addition of cold water (20 mL) at 0 °C. After removal of THF by evaporation under reduced pressure, 10% aqueous citric acid solution (15 mL) was added and extracted with ethyl acetate (50 mL × 2). The combined ethyl acetate layers were washed sequentially with saturated sodium bicarbonate (NaHCO3, 30 mL) and sodium chloride (NaCl, 30 mL) aqueous solutions and dried over anhydrous sodium sulfate (Na2SO4). Ethyl acetate was removed by evaporation under reduced pressure to give 0.86 g (100% yield) of 14 as a colorless oil.1H NMR (300 MHz, CDCl3) δ 4.40 (m, 1H), 3.85-3.70 (m, 3H), 2.13 (m, 1H), 1.90 (m, 1H), 1.42 (s, 9H).
References
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[2] Patent: US2009/68105, 2009, A1. Location in patent: Page/Page column 11
[3] Journal of Medicinal Chemistry, 1996, vol. 39, # 4, p. 817 - 825
[4] Angewandte Chemie - International Edition, 2013, vol. 52, # 30, p. 7829 - 7832
[5] Angew. Chem., 2013, vol. 125, # 30, p. 7983 - 7986,4
