反应详情

To a 22-L flask is added 526.4 g (3.07 mol) of 1-acetylpiperidine-4-carboxylic acid, 8 L of methylene chloride, and 55 mL of DMF. To the resultant heterogeneous suspension is added 508.9 g (3.13 mol) of carbonyl diimidazole in two portions at room temperature. After two hours, 583.5 g (3.07 mol) of 2-Amino-1-(4-fluoro-phenyl)-ethanone hydrochloride (J. Heterocylcic Chem (1987), 24, 297. ) is added and the resultant mixture is allowed to stir overnight. The reaction mixture is extracted with 2 N HCl (3×1 L), saturated sodium bicarbonate solution (3×1 L), brine (1×1 L), dried over sodium sulfate, and filtered. To the filtrate is added toluene and the solution is concentrated in-vacuo to ca. 100 mL and the resultant precipitate is filtered. The solid is dried in-vacuo at 60° C. for 18 h to give 800 g of 1-Acetyl-piperidine-4-carboxylic acid[2-(4-fluoro-phenyl)-2-oxo-ethyl]-amide as an off-white solid.

1. extractionThe reaction mixture is extracted with 2 N HCl (3×1 L), saturated sodium bicarbonate solution (3×1 L), brine (1×1 L)
2. dry with materialdried over sodium sulfate
3. filtrationfiltered
4. additionTo the filtrate is added toluene
5. concentrationthe solution is concentrated in-vacuo to ca. 100 mL
6. filtrationthe resultant precipitate is filtered
7. customThe solid is dried in-vacuo at 60° C. for 18 h