Sodium Hydroxide → 3-(7-Acetylamino-1-oxo-1,3-dihydro-isoindol-2-yl)-3-(4-difluoromethoxy-3-ethoxy-phenyl)-propionic acid
反応式
C[O:2][C:3](=[O:33])[CH2:4][CH:5]([N:19]1[CH2:27][C:26]2[C:21](=[C:22]([NH:28][C:29](=[O:31])[CH3:30])[CH:23]=[CH:24][CH:25]=2)[C:20]1=[O:32])[C:6]1[CH:11]=[CH:10][C:9]([O:12][CH:13]([F:15])[F:14])=[C:8]([O:16][CH2:17][CH3:18])[CH:7]=1.[OH-].[Na+]>C1COCC1>[C:29]([NH:28][C:22]1[CH:23]=[CH:24][CH:25]=[C:26]2[C:21]=1[C:20](=[O:32])[N:19]([CH:5]([C:6]1[CH:11]=[CH:10][C:9]([O:12][CH:13]([F:14])[F:15])=[C:8]([O:16][CH2:17][CH3:18])[CH:7]=1)[CH2:4][C:3]([OH:33])=[O:2])[CH2:27]2)(=[O:31])[CH3:30]参加物
4
反応物 2
生成物 1
試薬・触媒・溶媒 1
実験手順
To the THF solution of 3-(7-acetylamino-1-oxo-1,3-dihydro-isoindol-2-yl)-3-(4-difluoromethoxy-3-ethoxy-phenyl)-propionic acid methyl ester (2.5 g, 5.4 mmol) was added dropwise 10N NaOH (1 ml, 10 mmol) and was stirred at room temperature overnight. The resulted suspension was filtered and the solid was dissolved in water (20 ml). The aqueous solution was acidified to pH=4 to obtain a milky suspension. The suspension was extracted with EtOAc (50 ml×3). The organic layer was washed with water (50 ml×2), brine (30 ml), dried over Na2SO4 and concentrated to give white solid (2.3 g, 96% yield): mp 105-107° C.; 1HNMR (CDCl3): δ 1.42 (J=7.5 Hz, 3H, OCH2CH3), 2.22 (s, 3H), 3.11 (dd, J=5, 12 Hz, 1H, CH2), 3.25 (dd, J=10, 15 Hz, 1H, CH2), 4.08 (q, J=7.5 Hz, 2H, OCH2CH3), 4.12 (d, J=17.5 Hz, 1H, CH2N), 4.38 (d, J=17.5 Hz, 1H, CH2N), 5.81 (m, 1H, CHN), 6.55 (t, JH-F=75 Hz, 1H, CF2H), 6.96 (m, 3H, Ar), 7.13 (d, J=7.5 Hz, 1H, Ar), 7.45 (m, 1H, Ar), 8.43 (d, J=7.5 Hz, 1H, Ar), 10.25 (s, 1H, NHCO). 13CNMR (CDCl3): δ14.6, 24.8, 36.7, 46.8, 51.7, 64.9, 111.8, 111.3, 115.9, 117.1, 117.3, 118.0, 118.9, 120.1, 122.8, 133.5, 136.7, 137.8, 140.1, 141.2, 150.9, 169.47, 169.49, 173.5: Anal. Calcd. for C22H22F2N2O6+0.22H2O: C, 58.41; H, 5.00; N, 6.19. Found: C, 58.06, H, 4.92, N, 5.90.