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
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 95 °C
Procedure
The product of Step 1 (2.66 g, 11.2 mmol), 2-bromo-1,4-thiazole (1.00 ml, 11.2 mmol), Pd2(dba)3 (0.514 g, 0.561 mmol), X-phos (0.535 g, 1.122 mmol), and cesium carbonate (7.31 g, 22.4 mmol) were added to a dry flask. The flask was degassed with argon, then dioxane (25 ml) and water (2.5 ml) were added. 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 flash chromatography (EtOAc/hexane gradient) to afford 3-fluoro-5-(1,3-thiazol-5-yl)aniline (2.27 g, 9.49 mmol, 85% yield). MS APCI: [M+H]+ m/z 195.1. 1H NMR (500 MHz, DMSO-d6) δ 9.02 (s, 1H); 8.18 (s, 1H); 6.66-6.62 (m, 1H); 6.61-6.59 (m, 1H); 6.29-6.26 (m, 1H); 5.58 (s, 2H).
Workup
- customThe flask was degassed with argon
- additiondioxane (25 ml) and water (2.5 ml) were added
- 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 flash chromatography (EtOAc/hexane gradient)
Sources & evidence
- ORD record
- ord-5de489e3a52547f88b20e1ea9eb66cd9
- Source dataset
- uspto-grants-2014_06
- Patent number
- US08759366B2
Reaction notes
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