Phosphorus oxychloride → 5-Chloro-1,6-naphthyridine
Reaction equation
[N:1]1[C:10]2[CH:9]=[CH:8][NH:7][C:6](=O)[C:5]=2[CH:4]=[CH:3][CH:2]=1.O=P(Cl)(Cl)[Cl:14]>>[Cl:14][C:6]1[N:7]=[CH:8][CH:9]=[C:10]2[C:5]=1[CH:4]=[CH:3][CH:2]=[N:1]2Participants
3
Conditions
- Temperature
- 0 °C
Procedure
A solution of 1,6-naphthyridin-5(6H)-one (500 mg, 3.42 mmol) in POCl3 (10 mL) was stirred at 100° C. for 14 h. POCl3 was removed under reduced pressure. The residue was dissolved with DCM (40 mL), and the solution was stirred at 0° C. Then aqueous Na2CO3 was added cautiously to adjust pH to 6-7. Then the organic phase was separated from the aqueous phase, and the aqueous phase was extracted with EtOAc (4×15 mL). The combined organic layers were washed with brine (100 mL), dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to give 5-chloro-1,6-naphthyridine as a yellow solid (533 mg, yield 95%). ESI MS: m/z 165 [M+H]+.
Workup
- customPOCl3 was removed under reduced pressure
- dissolutionThe residue was dissolved with DCM (40 mL)
- additionThen aqueous Na2CO3 was added cautiously
- customThen the organic phase was separated from the aqueous phase
- extractionthe aqueous phase was extracted with EtOAc (4×15 mL)
- washThe combined organic layers were washed with brine (100 mL)
- dry with materialdried over anhydrous Na2SO4
- filtrationfiltered
- concentrationconcentrated under reduced pressure
Sources & evidence
- ORD record
- ord-2892bf42735c4cef907ecb90ffd4177c
- Source dataset
- uspto-grants-2016_02
- Patent number
- US09249162B2
Reaction notes
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