Reaction Steps
To a stirred solution of 4-(4-allyloxycarbonyl-2-amino-phenylamino)-piperidine-1-carboxylic acid tert-butyl ester (20.0 g, 53.27 mmol, 1.0 equiv; example 1/step 4) in toluene (200 mL) and N-ethyldiisopropylamine (17.21 g, 133.17 mol, 2.5 equiv) was added a solution of triphosgene (18.97 g, 63.92 mmol, 1.2 equiv) in toluene (200 mL) and the reaction mixture stirred at 70° C. for 1.5 h. The solvent was evaporated, the residue diluted with water and extracted with ethyl acetate. The combined organic fractions were washed with water and a sat. solution of NaCl, dried over Na2SO4 and concentrated by evaporation under reduced pressure. The crude material was further washed with a mixture of hexane/ethyl acetate (95:5) to yield 15.5 g (73%) of the title product as wvhite solid. 1H NMR (400 MHz, DMSO): δ 1.43 (s, 9H), 1.72 (d, J=10.8, 2H), 2.17-2.23 (m, 2H), 2.88 (br s, 2H), 4.09 (d, J=8.6 Hz, 2H), 4.38 (t, J=12.2 Hz, 1H), 4.77 (d, J=5.3 Hz, 2H), 5.26 (d, J=10.4 Hz, 1H), 5.40 (dd, J=17.2 Hz, J=1.4 Hz, 1H), 5.99-6.09 (m, 1H), 7.35 (d, J=8.4 Hz, 1H), 7.53 (d, J=1.3 Hz, 1H), 7.69-7.71 (m, 1H), 11.17 (s, 1H). 13C-NMR (100 MHz, DMSO): δ 28.04, 28.43, 50.32, 64.78, 78.79, 108.13, 109.18, 117.70, 121.69, 121.71, 122.67, 128.20, 132.81, 133.39, 153.78, 153.82, 165.36. MS (ISP): 402.2 [M+H]+.
