Dimethylformamide → 5-Nitro-2-(spiro[1-benzofuran-3,1'-cyclopropan]-4-yloxy)pyridine
Reaction equation
[C:1]12([C:7]3=[C:8]([OH:12])[CH:9]=[CH:10][CH:11]=[C:6]3[O:5][CH2:4]1)[CH2:3][CH2:2]2.CN(C)C=O.Cl[C:19]1[CH:24]=[CH:23][C:22]([N+:25]([O-:27])=[O:26])=[CH:21][N:20]=1>>[N+:25]([C:22]1[CH:23]=[CH:24][C:19]([O:12][C:8]2[C:7]3[C:1]4([CH2:4][O:5][C:6]=3[CH:11]=[CH:10][CH:9]=2)[CH2:3][CH2:2]4)=[N:20][CH:21]=1)([O-:27])=[O:26]Participants
4
Conditions
- Temperature
- 100 °C
Procedure
To a solution of spiro[1-benzofuran-3,1′-cyclopropan]-4-ol (Reference Intermediate 214, 70 mg) in dry N,N-dimethylformamide (2 ml) potassium carbonate (89 mg, 0.647 mmol) and then 2-chloro-5-nitropyridine (75 mg, 0.475 mmol) were added and the reaction mixture was stirred for 3 hours at 100° C. The reaction was quenched with brine (1 ml), diluted with water (2 ml) and extracted with ethyl acetate (3×10 ml). The organic layer was dried over sodium sulphate, filtered and evaporated. The residue was purified by flash chromatography (Biotage system) on silica gel using a 10 g SNAP column and cyclohexane to cyclohexane/ethyl acetate 9:1 as eluents affording the title compound as a white solid (100 mg).
Workup
- customThe reaction was quenched with brine (1 ml)
- additiondiluted with water (2 ml)
- extractionextracted with ethyl acetate (3×10 ml)
- dry with materialThe organic layer was dried over sodium sulphate
- filtrationfiltered
- customevaporated
- customThe residue was purified by flash chromatography (Biotage system) on silica gel using a 10 g SNAP column and cyclohexane to cyclohexane/ethyl acetate 9:1 as eluents
Sources & evidence
- ORD record
- ord-9d0c614b61bc4a61a8553cd391e8abb2
- Source dataset
- uspto-grants-2015_12
- Patent number
- US09216967B2
Reaction notes
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