1-(4-Bromo-phenyl)-2-pyridin-4-yl-ethanone

Synthesis

A THF (50 mL) solution of LDA (51 mL, 2 M solution of THF) was cooled to 0 °C under nitrogen protection. 4-Methylpyridine (9.5 g, 102 mmol) was added slowly and the reaction was kept for 30 min. Subsequently, the reaction system was cooled to -65 °C. In another round-bottom flask, 4-bromo-N-methoxy-N-methylbenzamide was dissolved in THF (50 mL) and cooled to -65 °C under nitrogen protection. A freshly prepared 4-methylpyridine anionic solution (1.2 eq.) was slowly added to the above cooled amide solution over 45 min. After continued stirring for 30 minutes, acetic acid (50 mL) was slowly added and the reaction mixture was gradually warmed to room temperature. The pH of the mixture was adjusted to 7 with base and subsequently extracted with ethyl acetate. The organic phase was washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated. The residue was recrystallized by a solvent mixture of petroleum ether and ethyl acetate (10:1, v/v) to give 1-(4-bromophenyl)-2-(4-pyridinyl)-ethanone (5.2 g, 92% yield) as a yellow solid. Mass spectrum (ESI) m/z = 276 [M + H]+.

References

[1] Patent: US2013/158031, 2013, A1. Location in patent: Paragraph 0180; 0181
[2] MedChemComm, 2013, vol. 4, # 2, p. 443 - 449