Tris(1,1-dimethylethyl)phosphine → Methyl 2-(2,6-difluoro-4-methoxy-phenyl)thiazole-4-carboxylate
Reaction equation
Br[C:2]1[S:3][CH:4]=[C:5]([C:7]([O:9][CH3:10])=[O:8])[N:6]=1.[F:11][C:12]1[CH:17]=[C:16]([O:18][CH3:19])[CH:15]=[C:14]([F:20])[C:13]=1B(O)O.[F-].[K+].C(P(C(C)(C)C)C(C)(C)C)(C)(C)C>O1CCCC1.O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:11][C:12]1[CH:17]=[C:16]([O:18][CH3:19])[CH:15]=[C:14]([F:20])[C:13]=1[C:2]1[S:3][CH:4]=[C:5]([C:7]([O:9][CH3:10])=[O:8])[N:6]=1Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 3
Conditions
- Temperature
- 100 °C
Procedure
To a solution of methyl 2-bromothiazole-4-carboxylate (3.27 mmol, 741 mg) in tetrahydrofuran (15 mL) and water (1.5 mL) was added 2,6-difluoro-4-methoxyphenylboronic acid (1.8 equiv., 5.88 mmol, 1160 mg) and potassium fluoride (3.3 equiv., 10.8 mmol, 627 mg). The mixture was degassed with nitrogen, then tris(dibenzylideneacetone)dipalladium(0) (0.2 equiv., 0.654 mmol, 617 mg) and tri-tert-butylphosphine (1.0 M in toluene; 0.4 equiv., 1.31 mmol, 1.3 mL) were added and the reaction mixture was heated under microwave at 100° C. for 30 minutes. The reaction mixture was concentrated and the residue was purified on silica eluted with 0 to 50% EtOAc in heptane to afford methyl 2-(2,6-difluoro-4-methoxy-phenyl)thiazole-4-carboxylate (2.40 mmol, 685 mg, 74% yield).
Workup
- customThe mixture was degassed with nitrogen
- concentrationThe reaction mixture was concentrated
- customthe residue was purified on silica
- washeluted with 0 to 50% EtOAc in heptane
Sources & evidence
- ORD record
- ord-0c202543724941d6853a27b6150abbbb
- Source dataset
- uspto-grants-2016_05
- Patent number
- US09328106B2
Reaction notes
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