Methyl Nicotinate → [2,2-Dimethyl-3-(3-oxo-3-pyridin-3-yl-propionyl)cyclobutyl]acetic acid tert-butyl ester

Participants

Reaction Conditions

Reaction Steps

Tert-butyl ester 7 (47.7 g, 199 mmol) and methyl nicotinate (27.3 g, 199 mmol) were dissolved in THF (1 L) and cooled to 5° C. KOBut (44.6 g, 398 mmol) was added in 4 portions over 1 h. The reaction was stirred at 0° C. for 2 h. The reaction was quenched with saturated NH4Cl (200 mL) and concentrated to an oil. The residue was dissolved in EtOAc and washed with saturated NH4Cl (300 mL×3). The combined aqueous layers were extracted with EtOAc (100 mL×2). The organic layers were combined and dried with brine and MgSO4 and concentrated in vacuo. The residue was purified by chromatography (hexane-EtOAc, 2:1 to 1:1). Diketone 9 (33.8 g, 49%) was obtained as a yellow crystalline solid; the methyl ester of 7 (16.2 g, 26%) and a mixture (1:1) of both esters (11.5 g, 17%) were also collected as yellow crystalline solids.

Provenance & Evidence