Diisopropylamine → (5-Bromo-2-fluoro-pyridin-3-yl)-(2-methoxy-phenyl)-methanone

Participants

Reaction Conditions

Reaction Steps

To a round bottom flask were added di-iso-propylamine (5 ml, 35 mmol), and anhydrous THF (40 ml). The solution was stirred at −78° C. for 5 minutes under nitrogen. Then a 2.5 M solution of n-butyl lithium in hexane (12 ml, 30 mmol) was added slowly and the resulting solution was allowed to stir at −78° C. for another 30 minutes. At this time 5-bromo-2-fluoro-pyridine (5 g, 28 mmol) was added dropwise and the solution was allowed to sir at −40° C. for 2 hours. Then 2, N-dimethoxy-N-methyl-benzamide (7.2 g, 37 mmol) in THF (10 ml) was added and the resulting mixture was stirred at −40° C. for another 2 hours. The reaction was then quenched with 10% citric acid (40 ml) and worked up with ethyl acetate, brine, dried with Na2SO4. Silica chromatography of the crude using a gradient of ethyl acetate and hexane afforded (5-bromo-2-fluoro-pyridin-3-yl)-(2-methoxy-phenyl)-methanone (1.9 g, 21% yield). 1H NMR (500 MHz, DMSO-d6) δ 3.64 (s, 3H), 7.14 (m, 1H), 7.18 (d, 1H), 7.65 (m, 2H), 8.38 (d, 1H), 8.58 (s, 1H).). MS: m/z 310+312 (M+H+).

Provenance & Evidence