Cesium carbonate → HCID 89692897, compound

Participants

Reaction Steps

In a 50 ml round bottom flask equipped with a magnetic stir bar and fitted with a nitrogen inlet, the XPhos (210.80 mg, 0.44 mmol) and the cesium carbonate (1.80 g, 5.52 mmol) were combined dry. This mixture was taken up in 1,4-dioxane (10.00 ml, 116.91 mmol) and the 2-bromo-4-fluoro-1-methyl-benzene 16a (1.04 g, 5.53 mmol) was added followed by the piperazine-1-carboxylic acid tert-butyl ester 16b (514.80 mg, 2.76 mmol). The mixture was stirred together under vacuum at room temperature for 10 min and then the system was flushed with nitrogen. The palladium(II) acetate (62.10 mg, 0.28 mmol) was added to the reaction in one portion and the reaction was warmed to 100° C. and was allowed to stir under nitrogen overnight. The reaction was cooled to room temperature and filtered through Celite, washing with ethyl acetate. The collected product solution was then concentrated under reduced pressure and the product was purified from the resultant dark brown oil using silica gel column chromatography, eluting a gradient of 100% heptanes to 50% ethyl acetate in heptanes. 4-(5-fluoro-2-methyl-phenyl)-piperazine-1-carboxylic acid tert-butyl ester 16c (451.00 mg, 1.53 mmol) was isolated as an off-white solid. LCMS (m/e)=295 (M+H).

Provenance & Evidence