Potassium Phosphate, Tribasic → [3-chloro-6-(2,2-difluoro-2-phenyl-ethylamino)-pyridin-2-yl]-acetic Acid Ethyl Ester
Reaction equation
[CH2:1]([O:3][C:4](=[O:14])[CH2:5][C:6]1[C:11]([Cl:12])=[CH:10][CH:9]=[C:8](Cl)[N:7]=1)[CH3:2].[F:15][C:16]([F:25])([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[CH2:17][NH2:18].[O-]P([O-])([O-])=O.[K+].[K+].[K+].C1(C2C=CC=CC=2)C=CC=CC=1P(C1CCCCC1)C1CCCCC1>CC([O-])=O.CC([O-])=O.[Pd+2]>[CH2:1]([O:3][C:4](=[O:14])[CH2:5][C:6]1[C:11]([Cl:12])=[CH:10][CH:9]=[C:8]([NH:18][CH2:17][C:16]([F:15])([F:25])[C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[N:7]=1)[CH3:2]Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 150 °C
Procedure
A mixture of (3,6-dichloro-pyridin-2-yl)-acetic acid ethyl ester (139 mg, 593 μmol), as prepared in the previous step, 2,2-difluoro-2-phenylethylamine (132.5 mg, 844 μmol) (see Example 8a), K3PO4 (317 mg, 1.50 mmol) (Fluka, Catalog # 04347), Pd(OAc)2 (5.8 mg, 26 μmol), biphenyl-2-yl-dicyclohexyl-phosphane (22 mg, 62 μmol) (Strem) was taken up in dry, argon-sparged dioxane (650 μL), and the mixture was sealed under a blanket of argon. The yellowish heterogeneous mixture was microwaved with stirring (Smith Synthesizer) at 150° C. for 20 min, and the resulting amber-red heterogeneous mixture was diluted with 8 mL ether, filtered, and concentrated. Flash silica chromatography of the residue (6:1 hexanes/EtOAc eluent) afforded the title compound as a light yellow oil (128 mg, 61%).
Workup
- customin dry
- customargon-sparged dioxane (650 μL)
- customthe mixture was sealed under a blanket of argon
- customThe yellowish heterogeneous mixture was microwaved
- additionthe resulting amber-red heterogeneous mixture was diluted with 8 mL ether
- filtrationfiltered
- concentrationconcentrated
Sources & evidence
- ORD record
- ord-1449c76ce436481493f6f49c22dc07cf
- Source dataset
- uspto-grants-2010_11
- Patent number
- US07829584B2
Reaction notes
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