Bromide ion → 2,2-Dimethyl-3-(pyridin-4-yl)propanal

Participants

Reaction Conditions

Reaction Steps

4-(Bromomethyl)pyridine hydrobromide (5.00 g, 19.8 mmol) was suspended in ethyl acetate (40 mL) and water (20 mL) and washed with 10% aq. NaHCO3 solution (35 mL) to generated the free base. The layers were partitioned and the organic portion was concentrated and redissolved in benzene (30 mL). To this solution was added tetrabutylammonium iodide (112 mg, 0.303 mmol) and isobutyraldehyde (1.10 g, 15.2 mmol). The solution of aledyde and bromide was then added via addition funnel in dropwise fashion over a period of 30 minutes to a stirred suspension of powdered NaOH (608 mg, 15.2 mmol) in benzene (90 mL) at 60° C. The reaction was stirred at 60° C. for 5 hours then cooled to ambient temperature. EtOAc (40 mL) was added and the reaction mixture was washed with water (40 mL), satd. aq. sodium bisulfite solution (2×25 mL), then brine (30 mL). The organic portion was dried (Na2SO4) and concentrated. Purification of the resulting oily residue by flash chromatography (gradient elution: hexanes then 7% EtOH/hexanes) provided the title compound (608 mg, 3.73 mmol) as a off-yellow waxy solid.

Provenance & Evidence