Potassium Carbonate → 2-(3-Methoxy-4-methylphenoxy)-5-nitropyridine
Reaction equation
[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][C:3]=1[O:9][CH3:10].C(=O)([O-])[O-].[K+].[K+].Cl[C:18]1[CH:23]=[CH:22][C:21]([N+:24]([O-:26])=[O:25])=[CH:20][N:19]=1>CN(C)C=O>[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:18]2[CH:23]=[CH:22][C:21]([N+:24]([O-:26])=[O:25])=[CH:20][N:19]=2)=[CH:4][C:3]=1[O:9][CH3:10]Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 115 °C
Procedure
To a solution of 4-methyl-3-(methyloxy)phenol (Reference Intermediate R2, 400 mg) in dry N,N-dimethylformamide (15 mL), potassium carbonate (1200 mg, 8.69 mmol) and then 2-chloro-5-nitropyridine (551 mg, 3.47 mmol) were added and the reaction mixture was stirred for 2 hours at 115° C. The reaction was quenched with water (10 mL), diluted with brine (20 mL) and extracted with ethyl acetate (3 times 30 mL). The organic layer was washed with ice cold brine (2 times 30 mL), dried over sodium sulphate, filtered and evaporated. The residue was purified by silica gel chromatography (Biotage system, 100 g SNAP column) with a gradient cyclohexane/ethyl acetate from 10/0 to 8/2. Evaporation afforded the to title compound as a light yellow oil (570 mg).
Workup
- customThe reaction was quenched with water (10 mL)
- additiondiluted with brine (20 mL)
- extractionextracted with ethyl acetate (3 times 30 mL)
- washThe organic layer was washed with ice cold brine (2 times 30 mL)
- dry with materialdried over sodium sulphate
- filtrationfiltered
- customevaporated
- customThe residue was purified by silica gel chromatography (Biotage system, 100 g SNAP column) with a gradient cyclohexane/ethyl acetate from 10/0 to 8/2
- customEvaporation
Sources & evidence
- ORD record
- ord-070be5524d804097865fb243966ad46c
- Source dataset
- uspto-grants-2016_05
- Patent number
- US09346790B2
Reaction notes
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