Potassium Hydroxide → 3-({4-[(4-Acetyl-3-hydroxy-2-methyl-phenylamino)-methyl]-phenyl}-hydroxy-methyl)-benzoic acid
Reaction equation
[C:1]([C:4]1[CH:9]=[CH:8][C:7]([NH:10][CH2:11][C:12]2[CH:17]=[CH:16][C:15]([CH:18]([OH:27])[C:19]3[CH:20]=[C:21]([CH:24]=[CH:25][CH:26]=3)[C:22]#N)=[CH:14][CH:13]=2)=[C:6]([CH3:28])[C:5]=1[OH:29])(=[O:3])[CH3:2].[OH-:30].[K+].CCO.[OH2:35]>>[C:1]([C:4]1[CH:9]=[CH:8][C:7]([NH:10][CH2:11][C:12]2[CH:17]=[CH:16][C:15]([CH:18]([OH:27])[C:19]3[CH:20]=[C:21]([CH:24]=[CH:25][CH:26]=3)[C:22]([OH:35])=[O:30])=[CH:14][CH:13]=2)=[C:6]([CH3:28])[C:5]=1[OH:29])(=[O:3])[CH3:2]Participants
Conditions
- Temperature
- 150 °C
Procedure
To 3-({4-[(4-Acetyl-3-hydroxy-2-methyl-phenylamino)-methyl]-phenyl}-hydroxy-methyl)-benzonitrile (160 mg, 0.41 mmol) in EtOH/H2O (6:1, 2.1 mL) in a microwave tube is added powdered KOH (140 mg, 2.0 mmol). The tube is sealed, placed in a microwave reactor, and heated at 150° C. for 30 min. The reaction mixture is acidified to pH=7 and concentrated. The residue is purified by reverse phase HPLC using 90:10 to 20:80 (H2O/0.1% TFA)/CH3CN. Obtained is the title compound as a brownish solid (86 mg, 52%). LC-MS (m/e): 404 (M−1); 1H NMR (DMSO-d6) δ 13.16 (1H, s), 12.85 (1H, bs), 7.90 (1H, m), 7.73 (1H, m), 7.56 (1H, m), 7.32-7.45 (2H, m), 7.27 (2H, d), 7.20 (2H, d), 6.76 (1H, t), 6.00 (1H, d), 5.69 (1H, s), 4.38 (2H, d), 2.35 (3H, s), 1.93 (3H, s).
Workup
- customThe tube is sealed
- customplaced in a microwave reactor
- concentrationconcentrated
- customThe residue is purified by reverse phase
- customObtained
Sources & evidence
- ORD record
- ord-c55d49162f0c469da35c2667d0592520
- Source dataset
- uspto-grants-2010_10
- Patent number
- US07816523B2
Reaction notes
Loading…