Reaction #1833279

Reaction equation

methyl 6-methylnicotinate

NaH

toluene

methyl 6-methylnicotinate ethyl acetate

methyl 6-methylnicotinate ethyl acetate

→

2-methyl-5-acetylpyridine

Yield 65.0%

Solvents

water

ethyl acetate

DMF

Conditions

Workup

1. 1
   workup.ADDITIONwas added
2. 2
   workup.ADDITIONAfter addition
3. 3
   workup.WAITthe reaction was conducted at 80° C. for 8 h
4. 4
   Temperaturecooled to room temperature
5. 5
   Extractionthe water layer was extracted with ethyl acetate three times, 200 ml per time
6. 6
   Otherto evaporate ethyl acetate
7. 7
   workup.ADDITION10% H2SO4 aqueous solution 400 ml was added
8. 8
   Temperatureheated to 110° C.
9. 9
   Temperaturerefluxed for 2 h
10. 10
    Temperaturecooled to room temperature
11. 11
    Filtrationto 9, suction filtration
12. 12
    Washthe filter cake was washed with ethyl acetate
13. 13
    ExtractionThe filtrate was extracted with ethyl acetate four times
14. 14
    Otherrotary evaporated
15. 15
    Otherto dry

Procedure

50 g of methyl 6-methylnicotinate was dissolved in 200 ml of ethyl acetate; 60% NaH 26.5 g, toluene 400 ml and DMF 34 ml were added to a three-necked bottle, 10% methyl 6-methylnicotinate ethyl acetate solution 20 ml was added, heated to 80° C., stirred for 0.5 h. To the reaction bottle, the residual methyl 6-methylnicotinate ethyl acetate solution was added dropwise slowly within about 1.5 h. After addition, the reaction was conducted at 80° C. for 8 h. The reaction stopped, cooled to room temperature. 300 ml of water was added to the reaction bottle, skimmed, the water layer was extracted with ethyl acetate three times, 200 ml per time. All ethyl acetate layers were combined, distillated at a reduced pressure to evaporate ethyl acetate, then 10% H2SO4 aqueous solution 400 ml was added, heated to 110° C., refluxed for 2 h. The reaction was then stopped, cooled to room temperature. Solid K2CO3 was used to adjust PH to 9, suction filtration was performed, the filter cake was washed with ethyl acetate. The filtrate was extracted with ethyl acetate four times, combined and rotary evaporated to dry, to obtain 35 g of 2-methyl-5-acetylpyridine, yield was about 65%.

Source