Reaction #158273

Reaction equation

2-(4-chlorophenyl)propanoic acid

n-butyllithium

1-Bromo-3-chloropropane

→

title compound

Yield 83.5%

5-chloro-2-(4-chlorophenyl)-2-methylpentanoic acid

Yield 83.5%

Solvents

THF

Conditions

Workup

1. 1
   ExtractionThe reaction mixture was extracted with 1N aqueous sodium hydroxide solution (2×100 mL)
2. 2
   ExtractionThe mixture was extracted with ethyl acetate (3×100 mL)
3. 3
   Dryingthe extract was dried over magnesium sulfate
4. 4
   Otherthe solvent was evaporated under reduced pressure
5. 5
   OtherThe residue was purified by silica gel column chromatography (ethyl acetate/hexane)

Procedure

Under a nitrogen atmosphere, to a mixture of 2-(4-chlorophenyl)propanoic acid (13.3 g) in THF (140 mL) was added n-butyllithium (1.6M hexane solution, 90.3 mL) at −60° C. to —70° C., and the mixture was allowed to warm to −20° C. 1-Bromo-3-chloropropane (11.4 g) was added to the reaction mixture at −20° C. to 10° C., and the mixture was stirred at room temperature for 12 hr. The reaction mixture was extracted with 1N aqueous sodium hydroxide solution (2×100 mL), and the extract was acidified with 3N hydrochloric acid (100 mL). The mixture was extracted with ethyl acetate (3×100 mL), the extract was dried over magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (15.7 g).

Source