Morpholine → 4-(6-Bromopyridin-3-yl)morpholine

Temperature

20 °C

Pd2(dba)3 (0.564 g, 0.62 mmol) was added to 2-bromo-5-iodopyridine (5.00 g, 17.61 mmol), morpholine (1.541 mL, 17.61 mmol), sodium tert-butoxide (4.23 g, 44.03 mmol) and Xantphos (1.019 g, 1.76 mmol) in toluene (200 mL) at 20°C. The resulting solution was stirred at r.t. for 3 days (as the reaction was started on a Friday). Complete. The reaction mixture was diluted with EtOAc (100 mL), and washed sequentially with water (100 mL) and saturated brine (100 mL). The organic layer was dried with MgSO4, filtered and evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 0 to 100% (EtOAc:MeOH - 10:1) in heptane. Pure fractions were evaporated to dryness LCMS indicated some di-substituted product present. Triturated in heptane:EtOAc, filtered and dried to afford 4-(6-bromopyridin-3-yl)morpholine (2.400 g, 56.1 %) as a beige solid.

ORD record

ord-e0d3875cf2584a84afda6341abdff6dc

Source dataset

750 AstraZeneca ELN dataset

Original link

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