Triethylamine → HCID 67409328, Verbindung

Beteiligte Stoffe

Reaktionsschritte

To a solution of tert-butyl 2,7-diazaspiro[3.5]nonane-7-carboxylate hydrochloride (4.35 g. 16.6 mmol) and 5-(2H-1,2,3-triazol-2-yl)indan-1-one (SM-1h, 3.3 g, 16.6 mmol) in dichloromethane (50 mL) was added triethylamine (6.94 mL, 49.7 mmol) followed by titanium(IV) isopropoxide (9.81 mL, 33.1 mmol). The reaction was stirred at room temperature overnight and sodium triacetoxyborohydride (4.21 g, 19.8 mmol) was added. After stirring for 4 days, the reaction was quenched with saturated ammonium chloride. The mixture was diluted with 50 mL of dichloromethane and 50 mL water and filtered through a Celite® pad. The aqueous layer was extracted with dichloromethane (30 mL×2). The combined organic layers were washed with brine and dried over MgSO4. The solvent was concentrated and the crude material was chromatographed on a Combiflash ISCO purification system (Teledyne Corp., Lincoln, Nebr.) using an EtOAc/heptanes gradient. The enantiomers were separated via preparative chiral HPLC (Chiralcel OD-H, 250 mm×30 mm, flow-rate—100 g/min, 65/35 CO2/MeOH, with 0.1% IPA) to afford tert-butyl 2-((R)-5-(2H-1,2,3-triazol-2-yl)-2,3-dihydro-1H-inden-1-yl)-2,7-diazaspiro[3.5]nonane-7-carboxylate (6-1a, 1.58 g, 23%) as a white solid. MS (ES+) 410.5 (M+H)+. 1H NMR (CD3OD) δ 1.42 (s, 9H), 1.70-1.73 (m, 4H), 1.92-2.02 (m, 1H), 2.23-2.27 (m, 1H), 2.89-2.92 (m, 2H), 3.09-3.14 (m, 2H), 3.23-3.30 (m, 3H), 3.32-3.36 (m, 3H), 4.02-4.05 (m, 1H), 7.45 (d, 1H), 7.87 (s, 2H), 7.89-7.93 (m, 2H).

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