Methyl 4-oxo-1,4,5,6-tetrahydrocyclopenta[b]pyrrole-2-carboxylate → Methyl 4-(3,4-difluorobenzyl)-1,4,5,6-tetrahydrocyclopenta[b]pyrrole-2-carboxylate
反応式
O=[C:2]1[C:9]2[CH:8]=[C:7]([C:10]([O:12][CH3:13])=[O:11])[NH:6][C:5]=2[CH2:4][CH2:3]1.[F:14][C:15]1[CH:16]=[C:17]([CH:21]=[CH:22][C:23]=1[F:24])[CH2:18][Mg]Br>[Pd]>[F:14][C:15]1[CH:16]=[C:17]([CH:21]=[CH:22][C:23]=1[F:24])[CH2:18][CH:2]1[C:9]2[CH:8]=[C:7]([C:10]([O:12][CH3:13])=[O:11])[NH:6][C:5]=2[CH2:4][CH2:3]1参加物
4
実験手順
The title compound was synthesized from methyl 4-oxo-1,4,5,6-tetrahydrocyclopenta[b]pyrrole-2-carboxylate in two steps. First, methyl 4-oxo-1,4,5,6-tetrahydrocyclopenta[b]pyrrole-2-carboxylate (0.60 g, 3.35 mmol) was reacted with 3,4-difluorobenzylmagnesium bromide (0.25 M in diethyl ether, 33.5 mL, 8.4 mmol) according to General Procedure 3. The resulting olefin was then converted to the title compound by hydrogenation according to General Procedure 6 (5% Pd on carbon). The crude product was purified by column chromatography (Isco CombiFlash) eluting with a gradient of 0-40% EtOAc/heptane to afford the title compound: 0.100 g. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.98-2.18 (m, 1 H) 2.48-2.64 (m, 1H) 2.64-2.83 (m, 4H) 3.27 (quin, J=7.00 Hz, 1H) 3.81 (s, 3H) 6.29-6.41 (m, 1H) 6.89 (ddd, J=6.19, 4.14, 2.03 Hz, 1H) 6.94-7.14 (m, 2H) 9.01 (br. s, 1H).