5-Bromo-2-fluoropyridine → 1-Tert-butyl-4-(6-fluoropyridin-3-yl)piperazine

Participants

Reaction Conditions

Reaction Steps

1-tert-Butylpiperazine (1.61 g, 11.4 mmol) is placed in 35 ml of toluene under nitrogen, 5-Bromo-2-fluoropyridine (2 g, 11.4 mmol), sodium t-butoxide (1.6 g, 17 mmol), tris(dibenzylideneacetone)dipalladium (0.52 g, 0.57 mmol), and S-Phos (0.93 g, 17 mmol) are then added. The reaction medium is heated at 80° C. for 18 h. After hydrolysis, and extraction with ethyl acetate, the organic phase is washed with water and then with a saturated aqueous sodium chloride solution. After drying over MgSO4, and concentrating to dryness, the crude product obtained is chromatographed on silica gel, elution being carried out with a gradient of methanol in dichloromethane ranging from 0% to 5%. 1.92 g of 1-tert-butyl-4-(6-fluoropyridin-3-yl)piperazine are obtained.

Provenance & Evidence