Butanal → 1-(6-Bromopyridin-2-yl)butan-1-ol

Participants

Reaction Steps

A solution of 2,6-dibromopyridine (1.00 g, 4.22 mmol) in THF (40 mL) was cooled to −78° C. (dry-ice/acetone bath) and treated with nBuLi (2.64 mL of a 1.6M solution in hexanes, 4.22 mmol) drop-wise over 10 minutes under nitrogen. After 30 minutes at this temperature the pale yellow/green solution was treated with butyraldehyde (400 μL, 4.44 mmol) drop-wise over 5 minutes and the resulting orange/red solution stirred at this temperature for 1 hour. The solution was then allowed to warm slowly to 0° C. (ice/water bath) over 20 minutes and was then quenched by the drop-wise addition of aqueous HCl (2M, 4 mL). The resulting pale yellow solution was reduced to an oil, partitioned between EtOAc (100 mL) and aqueous HCl (2M, 100 mL), and the layers separated. The aqueous was re-extracted with EtOAc (100 mL) and the combined organic layer washed with water (150 mL), brine (150 mL), dried (MgSO4), filtered and reduced to an orange/yellow oil. Purification by SPE (silica) eluting with cyclohexane:EtOAc (gradient 100:1 to 2:1) afforded the title compound (626 mg).

Provenance & Evidence