Reaction #939046

Reaction equation

Isobutyl bromide

ethyl 3-cyano-4-hydroxybenzoate

potassium carbonate

→

desired compound

Yield 33.0%

Ethyl 3-Cyano-4-isobutylbenzoate

Yield 33.0%

Solvents

DMF

Conditions

Workup

1. 1
   Temperaturecooled to room temperature
2. 2
   ExtractionThe aqueous mixture was extracted with ethyl acetate (200 mL×2)
3. 3
   WashThe ethyl acetate portion was washed successively with water (500 mL×2) and aqueous saturated brine (200 mL)
4. 4
   Dryingdried over anhydrous sodium sulfate
5. 5
   workup.DISTILLATIONto distill the solvent off
6. 6
   OtherThe residue was purified by silica gel column chromatography (ethyl acetate/hexane=1/4)
7. 7
   workup.DISSOLUTIONThe resulting crystalline product was dissolved in ethyl acetate (50 mL)
8. 8
   Temperatureunder heating
9. 9
   workup.ADDITIONwas added to the mixture
10. 10
    workup.STIRRINGThe hexane solution was stirred
11. 11
    Temperaturecooled to room temperature
12. 12
    workup.STIRRINGfurther stirred for 10 min.
13. 13
    Temperatureunder cooling with ice
14. 14
    FiltrationThe precipitated crystalline product was collected by filtration
15. 15
    Washwashed successively with ethyl acetate/hexane (1/5, 60 mL) mixture and hexane (500 mL)
16. 16
    Otherdried in air

Procedure

Isobutyl bromide (56.1 mL, 512 mmol) was added to a suspension of the ethyl 3-cyano-4-hydroxybenzoate crude product (51.4 g) and potassium carbonate (70.8 g, 512 mmol) in dry DMF (200 mL), stirred at 100° C. for 10 hours, and cooled to room temperature. Ice-water (500 mL) was then added to the cooled suspension. The aqueous mixture was extracted with ethyl acetate (200 mL×2). The ethyl acetate portion was washed successively with water (500 mL×2) and aqueous saturated brine (200 mL), dried over anhydrous sodium sulfate, and placed under reduced pressure to distill the solvent off. The residue was purified by silica gel column chromatography (ethyl acetate/hexane=1/4). The resulting crystalline product was dissolved in ethyl acetate (50 mL) under heating. The mixture was kept hot, while hexane (100 mL) was added to the mixture. The hexane solution was stirred and cooled to room temperature, and further stirred for 10 min. under cooling with ice. The precipitated crystalline product was collected by filtration, washed successively with ethyl acetate/hexane (1/5, 60 mL) mixture and hexane (500 mL), and dried in air, to give 20.8 g (yield 33%) of the desired compound in the form of a pale yellow crystalline product.

Source