反应详情

温度

140 °C

A mixture of 2-carboxymethyl-piperidine-1-carboxylic acid tert-butyl ester (Beckett et al, J. Med. Chem., 563, 1969) (6.72 g, 28 mmol) and 3,4-difluoro-benzene-1,2-diamine (4.00 g, 28 mmol) in polyphosphoric acid (130 g) was heated at 140° C. for 7.5 h. The cooled reaction mixture was poured onto excess solid potassium carbonate and crushed ice. The resulting basic, aqueous solution was extracted with ethyl acetate (2×) and the combined organics were washed with brine, dried (Na2SO4) and the solvent removed in vacuo. The residue was triturated with diethyl ether, ethyl acetate and pentane to afford the title compound as a white solid (4.29 g, 62%).

1. customThe cooled reaction mixture
2. customcrushed ice
3. extractionThe resulting basic, aqueous solution was extracted with ethyl acetate (2×)
4. washthe combined organics were washed with brine
5. dry with materialdried (Na2SO4)
6. customthe solvent removed in vacuo
7. customThe residue was triturated with diethyl ether, ethyl acetate and pentane