Phosphorus oxychloride → 8-Chloro-2-methoxy-1,5-naphthyridine
Reaction equation
[CH3:1][O:2][C:3]1[N:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[NH:9][CH:8]=[CH:7][C:6]2=O.O=P(Cl)(Cl)[Cl:16]>>[Cl:16][C:6]1[CH:7]=[CH:8][N:9]=[C:10]2[C:5]=1[N:4]=[C:3]([O:2][CH3:1])[CH:12]=[CH:11]2Participants
3
Conditions
- Temperature
- 110 °C
Procedure
To the intermediate 6-methoxy-1,5-naphthyridin-4(1H)-one (15.0 g, 0.085 mol) was added POCl3(300 mL) dropwise under nitrogen atmosphere at RT. The reaction mixture was heated to 110° C. with constant stirring. After 12 h, the mixture was concentrated in vacuo and azeotroped with toluene (2×100 mL). The residue was dissolved in ice-water (100 mL) and adjusted pH of the solution to 7 using 10% NaHCO3 solution, and extracted with EtOAc (4×100 mL). The combined organic extracts were washed with water (2×100 mL), saturated NaCl solution (100 mL), dried (Na2SO4), filtered and concentrated in vacuo.
Workup
- concentrationthe mixture was concentrated in vacuo
- customazeotroped with toluene (2×100 mL)
- dissolutionThe residue was dissolved in ice-water (100 mL)
- extractionextracted with EtOAc (4×100 mL)
- washThe combined organic extracts were washed with water (2×100 mL), saturated NaCl solution (100 mL)
- dry with materialdried (Na2SO4)
- filtrationfiltered
- concentrationconcentrated in vacuo
Sources & evidence
- ORD record
- ord-c9caa45732d147a5acbf5d4829c91657
- Source dataset
- uspto-grants-2010_08
- Patent number
- US07776857B2
Reaction notes
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