Phosphorus oxychloride → Ethyl 4-chloro-6-methoxy-1,5-naphthyridine-3-carboxylate
Reaction equation
[CH2:1]([O:3][C:4]([C:6]1[C:15](=O)[C:14]2[C:9](=[CH:10][CH:11]=[C:12]([O:17][CH3:18])[N:13]=2)[NH:8][CH:7]=1)=[O:5])[CH3:2].P(Cl)(Cl)([Cl:21])=O>>[CH2:1]([O:3][C:4]([C:6]1[CH:7]=[N:8][C:9]2[C:14]([C:15]=1[Cl:21])=[N:13][C:12]([O:17][CH3:18])=[CH:11][CH:10]=2)=[O:5])[CH3:2]Participants
Procedure
A solution of 6-methoxy-4-oxo-1,4-dihydro-[1,5]naphthyridine-3-carboxylic acid ethyl ester (110.0 g, 407.67 mmol, 1.0 eq) in phosphorus oxychloride (650 mL) is refluxed for 4 hours. Then the reaction mixture is cooled to room temperature and the solvent is evaporated. The residue is poured into ice water and the resulting mixture is basified with 25% ammonium hydroxide to pH=8˜9 and extracted with ethyl acetate (3×500 mL). The combined organic layers are dried over sodium sulfate, filtered and evaporated to give a brown solid as crude product, which is then purified by column chromatography (silica gel, eluent: ethyl acetate:petroleum ether, 1:4, v/v) to afford 4-chloro-6-methoxy-[1,5]naphthyridine-3-carboxylic acid ethyl ester as a light yellow solid (78 g, 62% yield).
Workup
- customthe solvent is evaporated
- additionThe residue is poured into ice water
- extractionextracted with ethyl acetate (3×500 mL)
- dry with materialThe combined organic layers are dried over sodium sulfate
- filtrationfiltered
- customevaporated
- customto give a brown solid as crude product, which
- customis then purified by column chromatography (silica gel, eluent: ethyl acetate:petroleum ether, 1:4, v/v)
Sources & evidence
- ORD record
- ord-286040babaf3426793b690456fe04044
- Source dataset
- uspto-grants-2015_09
- Patent number
- US09133219B2
Reaction notes
Loading…