Synthesis
Example 28 - Preparation of Compound 23: The generalized method used for the synthesis of Cmpd 23 analogs is shown in Scheme 2. Scheme 2 involves the process of synthesizing intermediates 7 to 9 and compound 23. Synthesis of intermediate 7: 2-bromoacetaldehyde diethyl acetal (4.5 g, 22.9 mmol), morpholine (2.0 g, 22.9 mmol) and K2CO3 (6.34 g, 45.9 mmol, 2 equiv) were mixed and the reaction was stirred for 16 hours at 120°C. After completion of the reaction, it was cooled to room temperature, diluted with water (50 mL) and extracted with DCM (3 x 50 mL). The organic layers were combined, washed sequentially with saturated aqueous NaHCO3 (50 mL) and brine (50 mL), dried over Na2SO4, filtered and concentrated to give the crude product. The crude product was purified by silica gel column chromatography (100-200 mesh) using 0-50% EtOAc-hexane gradient elution to afford Intermediate 7 (2.6 g, 56%) as a light yellow liquid.1H NMR (CDCl3) δ: 4.64 (t, J=5.3 Hz, 1H), 3.63-3.70 (m, 6H), 3.50-3.58 (m, 2H ), 2.52-2.55 (m, 6H), 1.20 (t, J=7.0Hz, 6H).TLC (hexane solution in 60% EtOAc): Rf=0.50.
References
[1] Patent: WO2011/126903, 2011, A2. Location in patent: Page/Page column 78
[2] Patent: US2017/326125, 2017, A1. Location in patent: Paragraph 0297-0298
[3] Patent: WO2015/131080, 2015, A1. Location in patent: Paragraph 00472; 00473
[4] Comptes Rendus Hebdomadaires des Seances de l'Academie des Sciences, 1959, vol. 248, p. 2015
[5] Organic and Biomolecular Chemistry, 2011, vol. 9, # 17, p. 5930 - 5933
