Phosphorus oxychloride → 2-Chloro-7-methoxyquinoxaline
Reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[NH:9][C:8](=O)[CH:7]=[N:6]2.COC1C=C2C(N=CC(=O)N2)=CC=1.O=P(Cl)(Cl)[Cl:29]>>[Cl:29][C:7]1[CH:8]=[N:9][C:10]2[C:5](=[CH:4][C:3]([O:2][CH3:1])=[CH:12][CH:11]=2)[N:6]=1Participants
Procedure
A solution of 6-methoxyquinoxalin-2(1H)-one & 7-methoxyquinoxalin-2(1H)-one (3 g, 18.28 mmol) in POCl3 (20 ml) was refluxed for 3 h. The solvent was evaporated under reduced pressure and the residue was diluted with cold water. The aqueous solution was basified by solid sodium carbonate and extracted with ethyl acetate. The combine organic layer was dried over anhydrous sodium sulfate, filtered and evaporated under reduced pressure to get crude compound. The crude compound was purified by silica gel chromatography (20% ethyl acetate in pet ether) to afford mixture of regioisomers (3.7 g). 2 g of the above mixture was separated by SFC purification to afford 2-chloro-7-methoxyquinoxaline (0.7 g, 34.7%) and 2-chloro-7-methoxyquinoxaline (0.9 g, 44.6%) as off white solid.
Workup
- customThe solvent was evaporated under reduced pressure
- additionthe residue was diluted with cold water
- extractionextracted with ethyl acetate
- dry with materialThe combine organic layer was dried over anhydrous sodium sulfate
- filtrationfiltered
- customevaporated under reduced pressure
- customto get crude compound
- customThe crude compound was purified by silica gel chromatography (20% ethyl acetate in pet ether)
- customto afford
- additionmixture of regioisomers (3.7 g)
- custom2 g of the above mixture was separated by SFC purification
Sources & evidence
- ORD record
- ord-7ac033de7bd04b57b472a9bc91d2fa02
- Source dataset
- uspto-grants-2014_04
- Patent number
- US08691757B2
Reaction notes
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