Reaction #330966

Reaction equation

sodium methoxide

toluene

4-(2,3,4-trimethoxy-6-methylbenzoyl)-3-chloro-5-trifluoromethylpyridine

hexamethylphosphorous triamide

→

4-(2,3,4-trimethoxy-6-methylbenzoyl)-3-methoxy-5-trifluoromethylpyridine

Yield 64.0%

Solvents

Water

Conditions

Workup

1. 1
   Temperatureunder reflux
2. 2
   Temperaturewith heating for 30 minutes
3. 3
   Otherto terminate
4. 4
   Otherthe reaction
5. 5
   Extractionthe aqueous layer was extracted with ethyl acetate
6. 6
   DryingThen, the organic layer was dried over anhydrous sodium sulfate
7. 7
   Filtrationsubjected to filtration
8. 8
   workup.DISTILLATIONthe solvent was distilled off under reduced pressure
9. 9
   OtherThe crude product was purified by silica gel column chromatography

Procedure

16.4 g (304 mmol) of sodium methoxide was added to a toluene 150 ml solution of 18.5 g (47.5 mmol) of 4-(2,3,4-trimethoxy-6-methylbenzoyl)-3-chloro-5-trifluoromethylpyridine obtained in Step (c) and 16.6 ml (95.4 mmol) of hexamethylphosphorous triamide, followed by stirring under reflux with heating for 30 minutes. Water was added to terminate the reaction, and the aqueous layer was extracted with ethyl acetate. Then, the organic layer was dried over anhydrous sodium sulfate and subjected to filtration, and the solvent was distilled off under reduced pressure. The crude product was purified by silica gel column chromatography to obtain 11.7 g (yield: 64%) of 4-(2,3,4-trimethoxy-6-methylbenzoyl)-3-methoxy-5-trifluoromethylpyridine (melting point: 103 to 106° C.).

Source