Reaction Steps
5 ml (41.5 mmol, 178 eqv) of a 25% aq. NaOH-solution was added to a solution of 134.0 mg (233.1 μmol) 3-(3′,3″-Dibenzyl-4″-(cyanomethoxy)-2-isobutyl-1,1′:4′,1″-terphenyl-4-yl)propanenitrile (29) in 8 ml MeOH, 8 ml THF and 1 ml 1,4-dioxane. The resulting mixture was refluxed for 29 h and then cooled to 0° C. After adjusting the pH to 2 by adding 1 N aq. HCl-solution, which led to a white precipitate, brine was added and the mixture was extracted with THF. The comb. org. fractions were washed twice with brine, dried over MgSO4 and evaporated. Column chromatography (first CH2Cl2/MeOH (10+1), then EtOAc/HOAc (95+5)) yielded 16.2 mg (26.4 μmol, 11%) 1b as a white solid: Rf (CH2Cl2/MeOH (10+1)) 0.20; 1H NMR (500 MHz, d4-MeOH+d4-HOAc) δ 1.06 (d, 6H, J=6.62 Hz), 1.99 (m, 1H), 2.83 (d, 2H, J=7.25 Hz), 3.03 (t, 2H, J=7.57 Hz), 3.31 (t, 2H, J=7.57 Hz), 4.31 (s, 2H), 4.40 (s, 2H), 5.09 (s, 2H), 7.27 (m, 3H), 7.41 (d, 1H, J=2.21 Hz), 7.45-7.54 (m, 10H), 7.57-7.62 (m, 5H); 13C NMR (100 MHz, d4-MeOH+d4-HOAc) δ 20.86, 22.84, 30.58, 31.59, 31.61, 36.67, 39.95, 43.23, 92.03, 112.62, 126.74, 126.80, 126.87, 128.35, 129.28, 129.31, 129.32, 129.74, 130.13, 131.04, 131.14, 131.18, 131.39, 132.69, 135.83, 139.17, 140.21, 140.77, 141.26, 141.47, 142.30, 142.38, 142.94, 176.09, 176.14; LRMS (FAB) m/z 658 (16), 635 (19), 331 (16), 329 (38), 309 (15), 297 (13), 193 (10), 179 (14), 177 (100), 155 (48), 154 (14), 153 (26), 152 (23), 135 (52), 121 (18), 119 (100); HRMS (FAB) Calcd. for C41H40O5Na: 635.277345. Found: 635.277200. Lyophilization of 1b from NH4OH led to the corresponding Bisammonia salt: 1H NMR (500 MHz, d4-MeOH) δ 0.67 (d, 6H, J=6.62 Hz), 1.59 (m, 1H), 2.41 (d, 2H, J=7.41 Hz), 2.46 (t, 2H, J=8.04 Hz), 2.90 (t, 2H, J=8.20 Hz), 3.90 (s, 2H), 4.05 (s, 2H), 4.43 (s, 2H), 6.85-6.91 (m, 3H), 6.94 (d, 1H, J=1.89 Hz), 7.02-7.24 (m, 15H).
