Reaction #2028899

Reaction equation

n-Butyllithium

trans-4-propylcyclohexanecarboxylic acid chloride

ethyl acetate

diisopropylamine

→

3-oxo-3-(trans-4-propyl-cyclohexyl)-propionic acid ethyl ester

Yield 91.0%

Solvents

THF

THF

Conditions

Workup

1. 1
   Otherwas kept at −40° C.
2. 2
   workup.ADDITIONwere added dropwise
3. 3
   TemperatureAfter the reaction mixture had been slowly warmed up to room temperature
4. 4
   Otherit was quenched with a saturated aqueous solution of ammonium chloride
5. 5
   workup.ADDITIONWater (1,000 ml) was then added
6. 6
   Otherto give two layers
7. 7
   ExtractionThe water layer was extracted with toluene (500 ml) three times
8. 8
   Washthe combined organic layer was washed with water
9. 9
   Dryingdried over anhydrous magnesium sulfate
10. 10
    workup.DISTILLATIONThe solvent was distilled off under reduced pressure
11. 11
    OtherThe residue was purified by silica gel chromatography (silica gel: 300 g, eluent: toluene)

Procedure

THF (1,000 ml) was added to diisopropylamine (162.9 g) in a reaction vessel under an atmosphere of nitrogen. n-Butyllithium was added dropwise, while the solution was kept at −40° C. or lower, and the stirring was continued for 30 minutes. The solution was cooled at −65° C. or lower, and ethyl acetate (141.9 g) and then a THF (200 ml) solution of trans-4-propylcyclohexanecarboxylic acid chloride (2) (189.9 g) prepared in the first step were added dropwise. After the reaction mixture had been slowly warmed up to room temperature with stirring, it was quenched with a saturated aqueous solution of ammonium chloride. Water (1,000 ml) was then added to give two layers. The water layer was extracted with toluene (500 ml) three times, and the combined organic layer was washed with water and then dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure. The residue was purified by silica gel chromatography (silica gel: 300 g, eluent: toluene) to give 3-oxo-3-(trans-4-propyl-cyclohexyl)-propionic acid ethyl ester (3) (220 g) in 90% yield.

Source