Lithium Hydroxide → (3-{4-[2-(2,4-Dichloro-Phenoxy)-Ethylcarbamoyl]-5-Phenyl-Isoxazol-3-Yl}-Phenyl)-Acetic Acid

반응식

C[O:2][C:3](=[O:36])[CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([C:11]2[C:15]([C:16](=[O:29])[NH:17][CH2:18][CH2:19][O:20][C:21]3[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][C:22]=3[Cl:28])=[C:14]([C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)[O:13][N:12]=2)[CH:6]=1.[Li+].[OH-]>COCCOC.O>[Cl:28][C:22]1[CH:23]=[C:24]([Cl:27])[CH:25]=[CH:26][C:21]=1[O:20][CH2:19][CH2:18][NH:17][C:16]([C:15]1[C:11]([C:7]2[CH:8]=[CH:9][CH:10]=[C:5]([CH2:4][C:3]([OH:36])=[O:2])[CH:6]=2)=[N:12][O:13][C:14]=1[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)=[O:29]

참가 물질

실험 절차

The crude (3-{4-[2-(2,4-dichloro-phenoxy)-ethyl-carbamoyl]-5-phenyl-isoxazol-3-yl}-phenyl)-acetic acid methyl ester 51 is dissolved in DME (2 mL). A solution of 1 M LiOH in H2O (0.2 mL) and is added and the mixture is stirred overnight at room temperature. The mixture is concentrated, then acidified with 1 M HCl, extracted with EtOAc (10 mL), dried over MgSO4, filtered, concentrated and purified on reverse phase HPLC (H2O/MeCN gradient) to afford the title compound I1 as an off-white solid: 1H-NMR (400 MHz, CD3CN) δ=7.61 (s, 1H), 7.57 (m, 1H), 7.38 (m, 5H), 7.33 (d, J=2.4 Hz, 1H), 7.28 (m, 2H), 7.20 (dd, J=9.2, 2.8 Hz, 1H), 7.16 (t, J=5.2 Hz, NH), 6.90 (d, J=8.8 Hz, 1H), 4.04 (t, J=5.2 Hz, 2H), 3.63 (q, J=5.2 Hz, 2H), 3.59 (s, 2H). MS calculated for C26H21Cl2N2O5 (M+H+) 511.0, found 511.0.