Reaction #80477

Reaction equation

Potassium t-butoxide

isobutyraldehyde

diethyl succinate

→

2-carboethoxycarbonyl-4-methyl pentanoic acid

Solvents

t-butanol

t-butanol

Conditions

Workup

1. 1
   Temperatureunder reflux, for 2 h
2. 2
   OtherThe solvent was removed from the reaction mixture by evaporation under reduced pressure
3. 3
   ExtractionThe product was extracted with ethyl ether, Et2O (3×200 ml)
4. 4
   WashThe ether solution was washed with water (3×200 ml)
5. 5
   Extractionand the product was extracted with 10% Na2CO3 (4×200 ml)
6. 6
   Otherthe product was isolated by extraction with Et2O (4×150 ml)
7. 7
   WashThe ether layer was washed with water
8. 8
   Dryingdried over sodium sulfate
9. 9
   Otherevaporated
10. 10
    workup.DISSOLUTIONThe remaining oil was dissolved in ethanol (300 ml) and hydrogenated in the presence of 10% palladium on charcoal (3.0 g)
11. 11
    FiltrationThe resultant mixture was filtered through Celite
12. 12
    Otherthe solvent was evaporated

Procedure

Potassium t-butoxide, 24.7 g (0.35M), was dissolved in 200 ml of refluxing t-butanol. A mixture of isobutyraldehyde, 18.2 ml (0.20M) and diethyl succinate 41.55 ml (0.25M) was added to the t-butanol solution over 30 min. The reaction mixture was stirred under reflux, for 2 h. The solvent was removed from the reaction mixture by evaporation under reduced pressure and acidified with 2N HCl. The product was extracted with ethyl ether, Et2O (3×200 ml). The ether solution was washed with water (3×200 ml); and the product was extracted with 10% Na2CO3 (4×200 ml). The solution was acidified with conc. HCl solution and the product was isolated by extraction with Et2O (4×150 ml). The ether layer was washed with water, dried over sodium sulfate, and evaporated. The remaining oil was dissolved in ethanol (300 ml) and hydrogenated in the presence of 10% palladium on charcoal (3.0 g). The resultant mixture was filtered through Celite and the solvent was evaporated to yield 38.04 g 2-carboethoxycarbonyl-4-methyl pentanoic acid as a mixture of isomers in the form of an oil. The isolated monoethyl ester was further purified on silica gel by flash chromatography using as eluent mixture ethyl acetate: hexane:acetic acid (1:10:0.05, v/v).

Source