Pyridine → 3-Fluoro-2-formyl-5-(tetrahydro-2H-pyran-2-yloxy)phenyl trifluoromethanesulfonate
Reaction equation
[F:1][C:2]1[CH:9]=[C:8]([O:10][CH:11]2[CH2:16][CH2:15][CH2:14][CH2:13][O:12]2)[CH:7]=[C:6]([OH:17])[C:3]=1[CH:4]=[O:5].N1C=CC=CC=1.[O:24](S(C(F)(F)F)(=O)=O)[S:25]([C:28]([F:31])([F:30])[F:29])(=O)=[O:26]>ClCCl>[F:29][C:28]([F:31])([F:30])[S:25]([O:17][C:6]1[CH:7]=[C:8]([O:10][CH:11]2[CH2:16][CH2:15][CH2:14][CH2:13][O:12]2)[CH:9]=[C:2]([F:1])[C:3]=1[CH:4]=[O:5])(=[O:26])=[O:24]Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Procedure
To a mixture of 2-fluoro-6-hydroxy-4-(tetrahydro-2H-pyran-2-yloxy)benzaldehyde (3.60 g, 15.0 mmol) and pyridine (5.93 g, 75.0 mmol) in dichloromethane (50 mL) was added dropwise Tf2O (6.35 g, 22.5 mmol) at −15° C. After stirring at room temperature for 3 h, the reaction was quenched by addition of iced-brine (50 mL) and extracted with dichloromethane (2×50 mL). The combined organic layers were dried over anhydrous Na2SO4 and concentrated in vacuo. The residue was purified by column chromatography (EtOAc/PE=1/8) on silica gel to give the title compound as a white solid (3.77 g, Yield: 67.5%). 1H NMR (400 MHz, DMSO-d) δ 10.12 (s, 1H), 7.26-7.30 (m, 1H), 7.04 (s, 1H), 5.78 (s, 1H), 3.62-3.71 (m, 2H), 1.80-1.87 (m, 3H), 1.56-1.64 (m, 3H). MS (ESI) m/z=373 [M+H]+.
Workup
- customthe reaction was quenched by addition of iced-brine (50 mL)
- extractionextracted with dichloromethane (2×50 mL)
- dry with materialThe combined organic layers were dried over anhydrous Na2SO4
- concentrationconcentrated in vacuo
- customThe residue was purified by column chromatography (EtOAc/PE=1/8) on silica gel
Sources & evidence
- ORD record
- ord-cd0d0f6186ee4016ba3c785f5e99b04b
- Source dataset
- uspto-grants-2013_01
- Patent number
- US08343944B2
Reaction notes
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