Acetic Acid → 3-(3-Ethoxy-4-methoxyphenyl)-3-(1-oxoisoindolinyl)propanoic acid
Reaction equation
[NH2:1][CH:2]([C:7]1[CH:12]=[CH:11][C:10]([O:13][CH3:14])=[C:9]([O:15][CH2:16][CH3:17])[CH:8]=1)[CH2:3][C:4]([OH:6])=[O:5].[C:18]([OH:21])(=O)[CH3:19]>>[O:21]=[C:18]1[C:19]2[C:8](=[CH:7][CH:2]=[CH:3][CH:4]=2)[CH2:9][N:1]1[CH:2]([C:7]1[CH:12]=[CH:11][C:10]([O:13][CH3:14])=[C:9]([O:15][CH2:16][CH3:17])[CH:8]=1)[CH2:3][C:4]([OH:6])=[O:5]Participants
Procedure
A stirred mixture of phthalic dicarboxaldehyde (2.68 g, 20.0 mmol) and 3-amino-3-(3-ethoxy-4-methoxyphenyl)propionic acid (4.78 g, 20.0 mmol) in glacial acetic acid (50 mL) under nitrogen was heated to reflux for 5 minutes. The reaction mixture was then allowed to cool to room temperature and was concentrated in vacuo to afford a yellow solid. The crude product was recrystallized twice from refluxing ethanol (150 mL). The resulting solid was then dried in vacuo (60° C., <1 mm) to afford 4.4 g (62%) of 3-(1-oxoisoindolin-2-yl)-3-(3-ethoxy-4-methoxyphenyl)propionic acid as a white solid: mp 193.5°-194° C.; 1H NMR (DMSO-d6) δ12.40 (br s, 1H), 7.75-7.40 (m, 4H), 7.05-6.85 (m, 3H), 5.71 (m, 1H), 4.51 (d, J=17.7 Hz, 1H), 4.11 (d, J=17.7 Hz, 1H), 3.99 (m, 2H), 3.73 (s, 3H), 3.25-3.02 (m, 2H), 1.30 (t, J=6.9 Hz, 3H), 13 C NMR (DMSO-d6) δ171.9, 166.9, 148.5, 147.9, 141.7, 132.2, 131.6, 131.4, 127.9, 123.5, 122.9, 119.3, 111.8, 63.7, 55.4, 51.2, 46.3, 36.8, 14.7; Anal. Calcd. for C20H21NO5. Theoretical: C, 67.59; H, 5.96; N, 3.94. Found: C, 67.64; H, 5.97; N, 3.92.
Workup
- temperaturewas heated
- temperatureto reflux for 5 minutes
- concentrationwas concentrated in vacuo
- customto afford a yellow solid
- customThe crude product was recrystallized twice
- temperaturefrom refluxing ethanol (150 mL)
- customThe resulting solid was then dried in vacuo (60° C., <1 mm)
Sources & evidence
- ORD record
- ord-995eb65f54504e30a49944a15577af4d
- Source dataset
- uspto-grants-1997_12
- Patent number
- US05698579
Reaction notes
Loading…