Dimethylformamide → 3-Fluoro-5-(1-oxo-1,3-dihydro-isobenzofuran-5-yl)-pyridine-4-carbaldehyde
Reaction equation
[Li][CH2:2][CH2:3][CH2:4][CH3:5].C(N[CH:10]([CH3:12])[CH3:11])(C)C.Br[C:14]1[CH:15]=[N:16][CH:17]=[C:18]([F:20])[CH:19]=1.CN([CH:24]=[O:25])C.[C:26]([O-:29])(O)=[O:27].[Na+]>C1COCC1>[F:20][C:18]1[CH:17]=[N:16][CH:15]=[C:14]([C:5]2[CH:4]=[C:3]3[C:12](=[CH:10][CH:11]=2)[C:26](=[O:27])[O:29][CH2:2]3)[C:19]=1[CH:24]=[O:25]Participants
Reactant 5
Product 1
Reagents, catalysts & solvents 1
Procedure
n-BuLi (13.85 mL, 22.16 mmol) was added to a solution of diisopropylamine (3.16 mL, 22.16 mmol) in THF (50 mL) at −78° C. After 30 min, 3-bromo-5-fluoropyridine (3.0 g, 17.05 mmol) in THF (25 mL) was added dropwise. The mixture was stirred for 1 hr, and then DMF (3.96 mL, 51.1 mmol) was added dropwise. Saturated aqueous NaHCO3 was added and the cooling bath was removed. The mixture was shaken with ethyl acetate and the organic phase was washed with brine, dried over MgSO4, and concentrated in vacuo. The residue was purified by silica gel flash chromatography employing dichloromethane-methanol, 9:1 to give 3-fluoro-5-(1-oxo-1,3-dihydro-isobenzofuran-5-yl)-pyridine-4-carbaldehyde. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.81 (d, J=1.4 Hz, 1H), 8.83 (s, 1H), 10.17 (s, 1H)
Workup
- customthe cooling bath was removed
- stirringThe mixture was shaken with ethyl acetate
- washthe organic phase was washed with brine
- dry with materialdried over MgSO4
- concentrationconcentrated in vacuo
- customThe residue was purified by silica gel flash chromatography
Sources & evidence
- ORD record
- ord-e094975e23ec4295983ec8e9febc6db8
- Source dataset
- uspto-grants-2013_08
- Patent number
- US08519134B2
Reaction notes
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