Cesium carbonate → 3-Fluoro-5-(1,3-thiazol-5-yl)aniline
Reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:6]=[C:7](B2OC(C)(C)C(C)(C)O2)[CH:8]=1)[NH2:5].Br[C:19]1[S:20][CH:21]=[N:22][CH:23]=1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.C(=O)([O-])[O-].[Cs+].[Cs+]>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:1][C:2]1[CH:3]=[C:4]([CH:6]=[C:7]([C:19]2[S:20][CH:21]=[N:22][CH:23]=2)[CH:8]=1)[NH2:5]Participants
6
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 95 °C
Procedure
The product of Step 1 (2.66 g, 11.22 mmol), 2-bromo-1,4-thiazole (1.003 mL, 11.22 mmol), Pd2(dba)3 (0.514 g, 0.561 mmol), X-phos (0.535 g, 1.122 mmol), and cesium carbonate (7.31 g, 22.44 mmol) were added to a dry flask. Degassed with argon, then added dioxane (25 mL) and water (2.5 mL). The reaction mixture was degassed with argon for five minutes, and then heated to 95° C. After 16 hours, the reaction mixture was cooled, diluted with ethyl acetate, filtered through celite, and concentrated. The residue was purified by column chromatography on silica gel, eluting with ethyl acetate and hexanes to afford 3-fluoro-5-(1,3-thiazol-5-yl)aniline (2.27 g, 9.49 mmol, 85%). MS ESI: [M+H]+ m/z 195.1.
Workup
- customDegassed with argon
- customThe reaction mixture was degassed with argon for five minutes
- temperaturethe reaction mixture was cooled
- additiondiluted with ethyl acetate
- filtrationfiltered through celite
- concentrationconcentrated
- customThe residue was purified by column chromatography on silica gel
- washeluting with ethyl acetate and hexanes
Sources & evidence
- ORD record
- ord-5c2a627510b042b8b8af3848db8c87ad
- Source dataset
- uspto-grants-2014_06
- Patent number
- US08759366B2
Reaction notes
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