Potassium Carbonate → 2-(5-Fluoropyridin-2-yl)but-3-yn-2-ol

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Reaction Steps

This compound was prepared according to a procedure similar to that described in Procedure C. In a 100-mL 3-necked round-bottom flask, s-BuLi (1.3M in hexane 10 mL) was added dropwise into a solution of 2-bromo-5-fluoropyridine (1.76 g, 10.00 mmol, 1.00 equiv) in ethyl ether (20 mL) under −76° C. The resulting solution was stirred for 1 h, then 4-(trimethylsilyl)but-3-yn-2-one (1.54 g, 10.98 mmol, 1.10 equiv) was added. The resulting solution was stirred for 2 h at −76° C. The reaction was then quenched by the addition of 10 mL of NH4Cl (sat., aq.). The resulting solution was extracted with 3×20 mL of ethyl acetate and the organic layers combined. The resulting mixture was washed with 1×20 mL of brine. The mixture was dried over anhydrous sodium sulfate and concentrated under vacuum. This resulted in 2.2 g (crude) of 2-(5-fluoropyridin-2-yl)-4-(trimethylsilyl)but-3-yn-2-ol as brown oil. In a 50-mL round-bottom flask, potassium carbonate (2.8 g, 20.29 mmol, 2.19 equiv) was added batchwise into a solution of 2-(5-fluoropyridin-2-yl)-4-(trimethylsilyl)but-3-yn-2-ol (2.2 g, 9.27 mmol, 1.00 equiv) in methanol (25 mL). The resulting solution was stirred for 2 h at room temperature. When completed monitored by TLC and LCMS, solvent was concentrated under vacuum. The residue was diluted with 20 mL of water. The resulting solution was extracted with 3×20 mL of ethyl acetate and the organic layers combined. The resulting mixture was washed with 1×20 mL of brine. The solids were filtered out. The resulting solution was dried over anhydrous sodium sulfate and concentrated under vacuum, the residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1:10). This resulted in 700 mg (46%) of 2-(5-fluoropyridin-2-yl)but-3-yn-2-ol as a light brown solid.

Provenance & Evidence