Pyridine → t-Butyl isobutyrylacetate

Participants

Reaction Conditions

Reaction Steps

Meldrum's acid (80 g, 555 mmol) was dissolved in 600 mL of CH2Cl2 and cooled to 0° C. Freshly distilled pyridine (87.8 g, 1.11 mol) was added to the CH2Cl2 solution and then isobutyryl chloride (65.0 g, 610.5 mmol) was added to the mixture via a pressure equalizing addition funnel. The reaction was stirred at 0° C. for 1 hr and then warmed to rt and stirred for 2 hr. Then, the reaction was quenched with water (200 mL) and washed with 0.5 M HCl (×2), water (×1), and brine (×1). The organize layer was dried over MgSO4 and concentrated in vacuo. The crude product was azeotropically dried with benzene (250 mL), and then dissolved in 200 mL of benzene and 200 mL of tert-butanol was added. The resultant reaction was heated at reflux for 4 hr. After this period, the volatiles were removed in vacuo and the product then distilled on the high vacuum pump (bp 62-63° C., 0.1 mm Hg). The desired β-keto ester 1E was obtained (58.6 g, 315.5 mmol) in 57% yield as a clear, colorless, light oil.

Provenance & Evidence