Reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:11]2[CH:16]=[CH:15][C:14]([C:17](=[O:26])[CH2:18][C:19]([CH3:25])([CH3:24])[C:20]([O:22][CH3:23])=[O:21])=[CH:13][CH:12]=2)[CH:5]=[CH:6][C:7]=1[NH:8]C=O.Cl>CO>[NH2:8][C:7]1[CH:6]=[CH:5][C:4]([C:11]2[CH:12]=[CH:13][C:14]([C:17](=[O:26])[CH2:18][C:19]([CH3:24])([CH3:25])[C:20]([O:22][CH3:23])=[O:21])=[CH:15][CH:16]=2)=[CH:3][C:2]=1[F:1]Participants
Procedure
To a solution of methyl 4-[3′-fluoro-4′-(formylamino)-1,1′-biphenyl-4-yl]-2,2-dimethyl-4-oxobutanoate (1.21 g, 3.39 mmol) in methanol (10 mL) was added conc. HCl (3.5 mL), and the resulting solution was stirred at rt for 16 h. The mixture was then concentrated, diluted with water, and the acidity was adjusted to pH ˜7 by slow addition of saturated aqueous sodium bicarbonate solution. The mixture was then extracted with dichloromethane, and the combined organic layers were washed with saturated sodium chloride solution, dried over sodium sulfate, and concentrated under reduced pressure. The residue was then triturated with ethyl acetate/hexane to afford methyl 4-(4′-amino-3′-fluoro-1,1′-biphenyl-4-yl)-2,2-dimethyl-4-oxobutanoate (998 mg, 89%). LC-MS ret. time 3.11 min, m/z 329.9 (MH+); 1H NMR (300 MHz, CDCl3) δ 1.31 (s, 6H), 3.28 (s, 2H), 3.66 (s, 3H), 6.84 (t, 1H), 7.21-7.35 (m, 2H), 7.55 (d, 2H), 7.93 (d, 2H).
Workup
- concentrationThe mixture was then concentrated
- additiondiluted with water
- additionthe acidity was adjusted to pH ˜7 by slow addition of saturated aqueous sodium bicarbonate solution
- extractionThe mixture was then extracted with dichloromethane
- washthe combined organic layers were washed with saturated sodium chloride solution
- dry with materialdried over sodium sulfate
- concentrationconcentrated under reduced pressure
- customThe residue was then triturated with ethyl acetate/hexane
Sources & evidence
- ORD record
- ord-60e9608537f748319dc29b91b9c3c30d
- Source dataset
- uspto-grants-2008_09
- Patent number
- US07423156B2
Linked notes
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