N-(3-Formyl-2-pyridinyl)-2,2-dimethylpropanamide → HCID 178517374, compound

Participants

Reaction Conditions

Reaction Steps

To a cooled solution (−78° C.) of LDA (2.0 M, 251 mmol) in 600 mL THF was added ester 4-3 (prepared from cyclopropylacetic acid and methanolic HCl solution, 15 g, 131 mmol) gradually over 30 min. The reaction mixture was stirred for 30 min at −78° C. Aldehyde 4-2 (22.5 g, 109 mmol) in 40 mL THF was added. The reaction mixture was stirred at −78° C. for 1 hr, then was warmed up to room temperature over 1 hr and quenched with 200 mL NH4Cl (sat.). The mixture was extracted with ethyl acetate (×3). The combined organic layers were washed with water, brine and dried over MgSO4 and concentrated to give a viscous residue which was subsequently dissolved in 200 mL 3N HCl. The mixture was refluxed at 105° C. for 24 hr. After concentration, the residue was poured into 500 mL ice-water and quenched with K2CO3 gradually (pH=9) to yield a solid as the desired product 4-4, which was filtered and dried in vacuum.

Provenance & Evidence