1. J.F. Bonfanti, P. Muller, F. Doublet, J. Fortin, N. Lounis, WO2013164337.
2. t-Butyl-4-propioloylpiperidine-1-carboxylate (5) At 0 °C, NaOAc (1.4g, 16.9mmol) was added to a solution of t-butyl 4-[3-(trimethylsilyl)propioloyl]piperidine-1-carboxylate 4 (5.2g, 16.9mmol) in MeOH (60mL). After stirring for 45min. at 0 °C, TLC (heptane/EtOAc, 1:1) showed complete conversion. The solvent was removed in vacuo at 20 °C. After co-evaporation with CH2Cl2 the residue was triturated with CH2Cl2 (50mL). Solids were filtered off and washed with CH2Cl2. The filtrate was used as such in the following step. For analysis, a sample was evaporated and purified by flash column chromatography (heptane, 15% EtOAc). 1H-NMR (400MHz, CDCl3) 4.30–3.87 (m, 2H), 3.39 (s, 1H), 3.03–2.76 (m, 2H), 2.68–2.52 (m, 1H), 2.06–1.82 (m, 2H), 1.67–1.56 (m, 2H), 1.46 (s, 9H); MW[C13H19NO3] = 237.29 g/mol; MS (ESI) m/z = 182 (M-C4H8+H)+. E- and Z-t-Butyl 4-(2,3-dibromoacryloyl)piperidine-1-carboxylate, (E-6 and Z-6) A solution of crude t-butyl 4-propioloylpiperidine-1-carboxylate (obtained as described above) in CH2Cl2 (60mL) was added to a suspension of pyridinium tribromide (6.7g, 21.0mmol) in CH2Cl2 (100mL). After stirring at room temperature for 15min., all the solids had dissolved. Stirring was continued overnight. Aqueous Na2S2O5 (5%, 30mL) was added and the mixture was stirred until the orange color had disappeared. The aqueous layer was extracted with CH2Cl2 (2x15mL) and the combined organic layers washed with H2O (30mL) and dried over Na2SO4. The solvents were removed in vacuo to give 6.1g (15.3mmol, 91% over two steps) of a yellow oil. 1H-NMR analysis was in agreement with a mixture of E- and Z-t-butyl 4-(2,3-dibromoacryloyl)piperidine-1-carboxylate in the ratio 6:5. The mixture was used as such in the following step. 1H-NMR (400MHz, CDCl3) 8.13 (s, 0.46H), 6.86 (s, 0.54H), 4.24–3.98 (m, 2H), 3.30–3.23 (m, 0.46H), 3.18–3.11 (m, 0.54H), 2.99–2.70 (m, 2H), 1.96–1.90 (m, 1H), 1.88–1.76 (m, 1H), 1.68–1.54 (m, 2H), 1.46 (s, 9H); MW[C13H19Br2NO3] = 397.10 g/mol; MS (ESI) m/z = 418/420/422 (M+Na)+.