1,2-Dimethoxyethane → 5-Pyrimidin-2-yl-indan-1-one

Participants

Reaction Conditions

Reaction Steps

To a 500 mL round-bottomed flask was added 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)indan-1-one (SM-1a, 12.9 g, 35.0 mmol), 2-chloropyrimidine (4.00 g, 35.0 mmol) and 400 mL of dimethoxyethane. Dry nitrogen gas was bubbled through the solution for 10 minutes. Aqueous sodium carbonate (2M in water, 140 mmol) was added followed by Pd(dppf)Cl2 catalyst (100 mg, 0.12 mmol). The reaction mixture was degassed for another 15 minutes. The reaction was heated to 95° C. (silicon oil bath temperature) for 2 hours. A second aliquot of 2-chloropyrimidine (1 g, 8.73 mmol) and Pd(dppf)Cl2 (100 mg, 0.12 mmol) were added to the reaction and heating was continued for another 2 hours. The reaction was cooled to room temperature overnight and 200 mL of water was added. The mixture was filtered through a Celite® pad and the organic phase was separated. The aqueous phase was extracted with ethyl acetate. The combined organic phases were washed with brine, dried over anhydrous MgSO4 and evaporated to afford 13.2 g of an orange brown solid. This material was triturated with hexane to give 6.72 g of a light brown solid (SM-1b). The filtrate was concentrated and purified by silica chromatography (ethyl acetate/heptanes) on a Combiflash ISCO purification system (Teledyne Isco Inc., Lincoln, Nebr.) to afford another 600 mg of product (7.32 g, 98%). MS (ES+) 211.2 (M+H)+. 1H NMR (CDCl3) δ 2.77 (t, 2H), 3.24 (t, 2H), 7.28 (d, 1H), 7.87 (d, 1H), 8.48 (d, 1H), 8.57 (s, 1H), 8.87 (d, 2H).

Provenance & Evidence