Phosphorus oxybromide → 2-Bromo-5-isopropylsulfanyl-pyridine
Reaction equation
[CH:1]([S:4][C:5]1[CH:6]=[CH:7][C:8](O)=[N:9][CH:10]=1)([CH3:3])[CH3:2].P(Br)(Br)([Br:14])=O>CN(C=O)C>[Br:14][C:8]1[CH:7]=[CH:6][C:5]([S:4][CH:1]([CH3:3])[CH3:2])=[CH:10][N:9]=1Participants
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 95 °C
Procedure
DMF (5 mL) was added slowly to a stirred mixture of 5-isopropylsulfanylpyridin-2-ol (765.8 mg, 4.525 mmol) and POBr3 (5.189 g, 18.10 mmol) at ambient temperature. After 10 minutes, the reaction mixture was warmed to 95° C. for 1 hour. The reaction mixture was cooled to ambient temperature and quenched by the slow addition of ice. The aqueous layer was extracted with EtOAc (×3) and the combined organics washed with saturated aqueous NaHCO3 (×3), brine (×1), dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by column chromatography (ISCO Companion™, 80 g column, eluting with 0 to 20% EtOAc/Petroleum Ether, loaded in DCM) to give the sub-title product as an off-white solid (661 mg, 63% Yield, 65% purity). 1H NMR (400.0 MHz, DMSO) δ 1.24 (d, J=6.8 Hz, 6H), 3.58 (sept, 1H), 7.62 (d, J=8.0 Hz, 1H), 7.78 (dd, J=2.6, 8.4 Hz, 1H) and 8.37 (d, J=2.5 Hz, 1H) ppm; MS (ES+) 231.7.
Workup
- temperatureThe reaction mixture was cooled to ambient temperature
- customquenched by the slow addition of ice
- extractionThe aqueous layer was extracted with EtOAc (×3)
- washthe combined organics washed with saturated aqueous NaHCO3 (×3), brine (×1)
- dry with materialdried (MgSO4)
- filtrationfiltered
- concentrationconcentrated in vacuo
- customThe residue was purified by column chromatography (ISCO Companion™, 80 g column, eluting with 0 to 20% EtOAc/Petroleum Ether, loaded in DCM)
Sources & evidence
- ORD record
- ord-49eca7e607104d4784ac068ba9f554ab
- Source dataset
- uspto-grants-2015_08
- Patent number
- US09096584B2
Reaction notes
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