1-Acetylpiperazine → 4-(4-Acetylpiperazin-1-yl)-2-fluorobenzaldehyde

Participants

Reaction Conditions

Reaction Steps

Palladium(II) acetate (111 mg, 0.49 mmol), 2-dicyclohexylphosphino-2′,6′-di-i-propoxy-1,1′-biphenyl (469 mg, 0.98 mmol) and sodium tert-butoxide (4.88 g, 49.2 mmol) were combined and the flask was purged with nitrogen. A solution of 1-piperazin-1-ylethanone (4.1 g, 32 mmol) and 4-bromo-1-(dimethoxymethyl)-2-fluoro-benzene (6.13 g, 24.6 mmol) in 1,4-dioxane (82 mL) was then added and the reaction was stirred at 100° C. for 16 hours. The reaction was then filtered through diatomaceous earth and concentrated. The resulting residue was dissolved in 50 mL of THF and 50 mL of 1 N aqueous HCl was added and the reaction was stirred at ambient temperature for 16 hours. The reaction was then neutralized with saturated aqueous Na2CO3 and extracted with dichloromethane (×3), dried with MgSO4, concentrated and purified by silica gel column chromatography (0-10% methanol in dichloromethane) to give 4-(4-acetylpiperazin-1-yl)-2-fluoro-benzaldehyde (3.68 g, 60% yield). LCMS (m/z) ES+ 251 [M+1]+.

Provenance & Evidence