反应详情

4,5-Difluoro-benzene-1,2-diamine (1.00 g, 6.9 mmol) and 2-carboxymethyl-piperidine-1-carboxylic acid tert-butyl ester (Beckett et al, J. Med. Chem., 563, 1969) (1.69 g, 6.9 mmol) were heated at 120° C. with stirring, under argon for 4 h. A further portion of 2-carboxymethyl-piperidine-1-carboxylic acid tert-butyl ester (0.85 g) was added and heating was continued for a further 2 h. The cooled reaction mixture was diluted with ethyl acetate, washed with saturated aqueous sodium bicarbonate (2×) and brine, dried (MgSO4) and the solvent removed in vacuo. The residue was chromatographed (silica gel, 0-30% ethyl acetate-pentane) to give a yellow solid which was triturated with diethyl ether to afford the title compound as a pale brown solid (0.38 g, 15%).

1. temperatureheating
2. waitwas continued for a further 2 h
3. customThe cooled reaction mixture
4. washwashed with saturated aqueous sodium bicarbonate (2×) and brine
5. dry with materialdried (MgSO4)
6. customthe solvent removed in vacuo
7. customThe residue was chromatographed (silica gel, 0-30% ethyl acetate-pentane)
8. customto give a yellow solid which
9. customwas triturated with diethyl ether