Acetic Acid → 4-(1-(6-Fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl)ethyl)morpholine

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of diisopropylamine (Aldrich, redistilled, 99.95%, 0.813 mL, 5.80 mmol) in THF (10 mL) in 150 mL round-bottomed flask, nBuLi (Aldrich, 2.5 M in hexanes, 2.32 mL, 5.80 mmol) was added dropwise at 0° C. The mixture was stirred at 0° C. for 30 min. The mixture was cooled to −78° C. and 4-(1-(6-fluoropyridin-3-yl)ethyl)morpholine (1.02 g, 4.84 mmol) in a total of 3 mL of THF was added dropwise. The mixture was stirred at −78° C. for 45 min. Triisopropyl borate (Aldrich, 1.39 mL, 6.04 mmol) in a total of 3 mL THF was added dropwise at that temperature, then the cold bath was removed. The mixture was stirred at room temperature for 1 h 20 min. Pinacol (0.773 g, 6.54 mmol) in a total of 5 mL THF was added at once and the mixture was stirred at room temperature for 10 min. Acetic acid (0.291 mL, 5.08 mmol) in a total of 3 mL THF was added at once and the mixture was stirred at room temperature for 2 h. The mixture was filtered through a pad of Celite® (diatomaceous earth), and extracted with 1 N NaOH (2×50 mL). The aqueous phase was treated with 4 N HCl until a pH of about 6 to 7 while an ice-water bath was applied, then extracted with EtOAc (3×50 mL). The combined organic phases were dried over sodium sulfate, filtered and concentrated in vacuo to afford crude 4-(1-(6-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl)ethyl)morpholine (1.22 g, 75% yield) as a light brown viscous oil. This material was used in the next reaction without further purification.

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