Cesium fluoride → 4-hydroxy-4-[2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulen-8-yl]-piperidine-1-carboxylic acid tert-butyl ester

Participants

Reaction Conditions

Reaction Steps

8-(5,5-Dimethyl-[1,3,2]dioxaborinan-2-yl)-2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene (200 mg, 0.47 mmol), 4-oxo-piperidine-1-carboxylic acid tert-butyl ester (63 mg, 0.31 mmol), bis(1,5-cyclooctadiene)nickel(0) (17 mg, 0.063 mmol), 1,3-bis(2,6-diisopropylphenyl)imidazolium chloride (27 mg, 0.063 mmol) and cesium fluoride (81 mg, 0.53 mmol) were loaded into a reaction vial, which was then flushed with nitrogen. Dry toluene (3 mL) was then added and nitrogen was bubbled through the mixture for 15 min. before heating at 80° C. for 30 min. The reaction mixture was combined with a mixture from a similar reaction (same quantities of boronate ester and oxo-piperidine, half-quantities of nickel and imidazolium catalysts, heated for 19.5 h) and extracted with ethyl acetate. The organic extract was washed with saturated aqueous sodium bicarbonate followed by brine, then dried (Na2SO4) and concentrated in vacuo. The resultant residue was subjected to flash chromatography (SiO2, gradient 20-70% ethyl acetate in cyclohexane) to give 4-hydroxy-4-[2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulen-8-yl]-piperidine-1-carboxylic acid tert-butyl ester (100 mg). LCMS RT=4.73, [M+H]+=512.

Provenance & Evidence