Isatoic Anhydride → HCID 17604146, compound
Reaction equation
[C:1]12[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=1)[NH:6]C(=O)O[C:2]2=[O:3].[NH2:13][C:14]1[CH:23]=[CH:22][C:17]([C:18]([O:20][CH3:21])=[O:19])=[CH:16][CH:15]=1>>[NH2:6][C:7]1[CH:8]=[CH:9][CH:10]=[CH:11][C:1]=1[C:2]([NH:13][C:14]1[CH:15]=[CH:16][C:17]([C:18]([O:20][CH3:21])=[O:19])=[CH:22][CH:23]=1)=[O:3]Participants
Conditions
- Temperature
- 140 °C
Procedure
Isatoic anhydride (4.0 g, 24.5 mmol) and methyl 4-aminobenzoate were combined and heated at 140° C. for 4 hours. The reaction was cool to room temperature and purified by flash chromatography on silica gel, eluting with 90-100% CH2Cl2 in heptane, to afford methyl 4-(2-aminobenzamido)benzoate (5.2 g, 78%). 4-(2-(tert-butyldimethylsilyloxy)ethoxy)-3,5-dimethylbenzaldehyde (1.0 g, 3.30 mmol) and anhydrous CuCl2 (1.3 g, 9.90 mmol) were added to a solution of methyl 4-(2-aminobenzamido)benzoate (0.900 g, 3.30 mmol) in anhydrous EtOH (70 mL) and heated to reflux for 6 hours, before being cooled to room temperature and concentrated in vacuo. Purification by flash chromatography on silica gel, eluting with 5% MeOH in CH2Cl2, followed by further purification on silica gel, eluting with 30-100% EtOAc in heptane, afforded the title compound as a white solid (0.500 g, 34%). 1H-NMR (300 MHz, DMSO-d6): δ 8.18 (dd, J=7.9, 1.1 Hz, 1H), 7.88-7.93 (m, 3H), 7.75 (d, J=6.7 Hz, 1H), 7.57-7.62 (m, 1H), 7.50 (d, J=8.5 Hz, 2H), 7.03 (s, 2H), 4.82 (t, J=5.5 Hz, 1H), 3.84 (s, 3H), 3.60-3.72 (m, 4H), 2.07 (s, 6H). MS (APCI) m/z: 445 (M+H)+.
Workup
- temperatureThe reaction was cool to room temperature
- custompurified by flash chromatography on silica gel
- washeluting with 90-100% CH2Cl2 in heptane
Sources & evidence
- ORD record
- ord-ceced81356334c45aae8b96e43c79b57
- Source dataset
- uspto-grants-2015_02
- Patent number
- US08952021B2
Reaction notes
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