Tetrahydrofuran → 2-(6-Benzyloxy-pyridin-3-yloxy)-2-methyl-propionic acid ethyl ester

Participants

Reaction Steps

To an ice-cold solution of 0.5 g (2.48 mmol) 6-benzyloxy-3-hydroxypyridine (commercially available) in 5 mL tetrahydrofuran 0.12 g (2.7 mmol) sodium hydride (55% dispersion in mineral oil) was added in portions. After the vigorous gas evolution had ceased the reaction mixture was stirred for another 20 min., then 0.44 mL (3.0 mmol) ethyl-alpha-bromoisobutyrate (commercially available) were added dropwise. The light brown suspension was stirred for 23 h at room temperature and then poured into water. The aqueous phase was extracted three times with ethyl acetate and the combined organic layers were washed with brine, dried over magnesium sulfate and filtered. Silica gel was added to the filtrate and the slurry evaporated. The resulting solid is purified by silica gel chromatography using a MPLC system (CombiFlash Companion, Isco Inc.) eluting with a gradient of heptane:ethyl acetate (100:0 to 70:30) to give the product as a colorless oil (38%). MS (Turbo Spray): m/z=316.1 [M+H].

Provenance & Evidence