Reaction #52175

Reaction equation

Sodium hydride

ethyl bromide

tBuOK

tBuOK

Methyl phenylsulfonylacetate

→

2-ethyl-2-(phenylsulfonyl)Butanoic Acid

Solvents

THF

Water

water

Water

DCM

DMF

Conditions

Workup

1. 1
   Temperatureunder cooling with ice
2. 2
   Otherto terminate
3. 3
   Otherthe reaction
4. 4
   ExtractionAfter the extraction with ethyl acetate (10 ml×3)
5. 5
   Otherdried
6. 6
   Concentrationconcentrated under reduced pressure
7. 7
   OtherThe residue was purified by the silica gel column chromatography (hexane, hexane/ethyl acetate, 100/1)
8. 8
   Otherto obtain an intermediate product
9. 9
   workup.STIRRINGThe reaction mixture was stirred at room temperature for 4 days
10. 10
    workup.STIRRINGAfter stirring at room temperature for 9 days
11. 11
    ExtractionThe resultant mixture was extracted with water (10 ml)
12. 12
    ExtractionAfter the extraction with DCM (10 ml×3)
13. 13
    Otherdried
14. 14
    Concentrationconcentrated under reduced pressure to quantitatively obtain 481 mg of the intended compound

Procedure

Methyl phenylsulfonylacetate (0.64 ml, 4.0 mmol) was diluted with DMF (5 ml). Sodium hydride (384 mg, 16 mmol) and ethyl bromide (1.19 ml, 16 mmol) were added thereto under argon atmosphere. The mixture was stirred at room temperature overnight. Water was added to the reaction mixture under cooling with ice to terminate the reaction. After the extraction with ethyl acetate (10 ml×3), the organic layers were combined together, dried and concentrated under reduced pressure. The residue was purified by the silica gel column chromatography (hexane, hexane/ethyl acetate, 100/1) to obtain an intermediate product. The intermediate product (532 mg, 1.97 mmol) was dissolved in THF (4 ml). Water (70.9 μl, 3.84 mmol) and tBuOK (1.77 g, 15.8 mmol) were added to the obtained solution. The reaction mixture was stirred at room temperature for 4 days. Additional water (35.5 μl, 1.97 mmol) and tBuOK (1.55 g, 13.8 mmol) were added to the obtained solution. After stirring at room temperature for 9 days, the reaction mixture was diluted with DCM (10 ml). The resultant mixture was extracted with water (10 ml). pH of the aqueous layer was adjusted to 2. After the extraction with DCM (10 ml×3), the organic layers were combined together, dried and concentrated under reduced pressure to quantitatively obtain 481 mg of the intended compound.

Source