Diisopropylamine → 1-(2,6-Difluoropyridin-3-yl)ethanone

Participants

Reaction Steps

A solution of freshly distilled diisopropylamine (14.7 mL, 104.3 mmol) in 10 mL of anhydrous THF was cooled to −78° and treated with 1.6 M solution of n-BuLi in hexanes (64.0 mL, 102.5 mmol). The resulting solution naturally warmed to −20° and was maintained at −20° for 1.5 hours. The solution was cooled to −78° and 2,6 difluoro pyridine (37-1) was added dropwise. The reaction was continued with stirring for 2 hours at −78° C. before a solution of 9.7 mL (86.9 mmol) of the Weinryb amide was added in 20 mL of THF. The resulting solution was warmed to ambient temperature overnight before quenching with a brine solution. The mixture was extracted with EtOAc (3×), and the combined organic layers were washed with H2O (1×), brine (2×), dried over MgSO4, and concentrated in vacuo. The crude product was purified via flash silica gel chromatography (0-40% EtOAc/Hexane) to yield the desired product 37-2. 1H NMR (CDCl3): 2.68 (s, 3H), 6.95 (d, 1H), 8.50 (q, 1H).

Provenance & Evidence