Cesium fluoride → 4-Amino-3-chloro-6-(2-fluoro-3-methoxy-4-methylphenyl)pyridine-2-carboxylic acid, methyl ester
Reaction equation
[NH2:1][C:2]1[CH:7]=[C:6](Cl)[N:5]=[C:4]([C:9]([O:11][CH3:12])=[O:10])[C:3]=1[Cl:13].[F:14][C:15]1[C:20]([O:21][CH3:22])=[C:19]([CH3:23])[CH:18]=[CH:17][C:16]=1B(O)O.[F-].[Cs+]>C(COC)OC.O>[NH2:1][C:2]1[CH:7]=[C:6]([C:16]2[CH:17]=[CH:18][C:19]([CH3:23])=[C:20]([O:21][CH3:22])[C:15]=2[F:14])[N:5]=[C:4]([C:9]([O:11][CH3:12])=[O:10])[C:3]=1[Cl:13]Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 2
Conditions
- Temperature
- 85 °C
Procedure
A solution of 4-amino-3,6-dichloropyridine-2-carboxylic acid, methyl ester (0.24 g, 1.1 mmol), 2-fluoro-3-methoxy-4-methylphenyl boronic acid (0.30 g, 1.63 mmol) and cesium fluoride (3.0 g, 3.26 mmole) in dimethoxyethane (2 mL) and water (2 mL) was purged with a stream of nitrogen for 15 minutes before adding dichlorobis(triphenylphosphine) palladium (0.07 g, 0.1 mmol) and then heated to 85° C. for 2 hours. The reaction mixture was diluted with water (15 mL) and extracted with ethyl acetate (2×15 mL). The combined extracts were washed with brine, dried (sodium sulfate) and concentrated. The residue was purified by chromatography (33% ethyl acetate in hexanes) to give 4-amino-3-chloro-6-(2-fluoro-3-methoxy-4-methylphenyl)pyridine-2-carboxylic acid, methyl ester (0.08 g, 0.2 mmol): mp 95-96° C.
Workup
- extractionextracted with ethyl acetate (2×15 mL)
- washThe combined extracts were washed with brine
- dry with materialdried (sodium sulfate)
- concentrationconcentrated
- customThe residue was purified by chromatography (33% ethyl acetate in hexanes)
Sources & evidence
- ORD record
- ord-19f1f0946cac458a8cf084e74cdf2403
- Source dataset
- uspto-grants-2008_01
- Patent number
- US07314849B2
Reaction notes
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