Phosphorus oxychloride → 2-Chloro-7-methoxy-1,5-naphthyridine
Reaction equation
CO[C:3]1[CH:12]=[CH:11][C:10]2[C:5](=[CH:6][C:7]([O:13][CH3:14])=[CH:8][N:9]=2)[N:4]=1.P(Cl)(Cl)([Cl:17])=O>CN(C)C=O>[Cl:17][C:3]1[CH:12]=[CH:11][C:10]2[C:5](=[CH:6][C:7]([O:13][CH3:14])=[CH:8][N:9]=2)[N:4]=1Participants
4
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 0 °C
Procedure
A mixture of 2,7-dimethoxy-[1,5]naphthyridine (5.0 g, 26.29 mmol, 1.0 eq) and phosphorus oxychloride (4.9 mL, 52.58 mmol, 2.0 eq) in N,N-dimethylformamide (100 mL) is stirred at 0° C. for 1 hour then at 80° C. for 1 hour. The reaction mixture is cooled to 0° C., quenched with 10 mL of saturated sodium acetate aqueous solution and then stirred at 30° C. for 30 minutes. The mixture is extracted with ethyl acetate (3×60 mL). The combined organic layers are dried over sodium sulfate, filtered and concentrated to give a crude that is purified by column chromatography (silica gel, eluent: ethyl acetate:petroleum ether, 1:6, v/v) to afford 2-chloro-7-methoxy-[1,5]naphthyridine as a yellow solid (3.3 g, 64% yield).
Workup
- waitat 80° C. for 1 hour
- temperatureThe reaction mixture is cooled to 0° C.
- customquenched with 10 mL of saturated sodium acetate aqueous solution
- stirringstirred at 30° C. for 30 minutes
- extractionThe mixture is extracted with ethyl acetate (3×60 mL)
- dry with materialThe combined organic layers are dried over sodium sulfate
- filtrationfiltered
- concentrationconcentrated
- customto give a crude that
- customis purified by column chromatography (silica gel, eluent: ethyl acetate:petroleum ether, 1:6, v/v)
Sources & evidence
- ORD record
- ord-c0188d9008064eaba8a0320616d966a6
- Source dataset
- uspto-grants-2015_09
- Patent number
- US09133219B2
Reaction notes
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