Carbon Dioxide → 3-Chloro-5-cyclopropylbenzoic acid

HRID 19804Notes

Reaction equation

HRID 19804 reaction equation
Br[C:2]1[CH:7]=[C:6]([CH:8]2[CH2:10][CH2:9]2)[CH:5]=[C:4]([Cl:11])[CH:3]=1.[Li]CCCC.[C:17](=[O:19])=[O:18]>C1COCC1>[Cl:11][C:4]1[CH:3]=[C:2]([CH:7]=[C:6]([CH:8]2[CH2:10][CH2:9]2)[CH:5]=1)[C:17]([OH:19])=[O:18]

Participants

5

Reactant 3

HCID 280Carbon DioxideHCID 665209601-Bromo-3-chloro-5-cyclopropylbenzeneHCID 178418339Butyllithium

Product 1

HCID 685583713-Chloro-5-cyclopropylbenzoic acidYield 70%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 1-bromo-3-chloro-5-cyclopropylbenzene (300 mg, 1.30 mmol) at −78° C. in THF (5 ml) was added nBuLi (890 μl, 1.6M solution in hexane, 1.43 mmol) dropwise. The resulting solution was stirred at −78° C. for 10 min after which solid carbon dioxide was added and the reaction mixture was warmed to RT over 3 hours. The reaction mixture was quenched with water and then extracted with ether. The aqueous phase was then made acidic with 1N HCl and then extracted with ethyl acetate. The organic phases were combined, washed with brine, dried (MgSO4), filtered and concentrated in vacuo to give the desired product 3-chloro-5-cyclopropylbenzoic acid (178 mg, 70%) which did not require further purification. MS (ISP) 195.1 (M−H)−.

Workup

  1. additionwas added
  2. customThe reaction mixture was quenched with water
  3. extractionextracted with ether
  4. extractionmade acidic with 1N HCl and then extracted with ethyl acetate
  5. washwashed with brine
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-0e51a125eab742b29af011c56a4f3d66
Source dataset
uspto-grants-2010_06
Patent number
US07745477B2

Reaction notes

Loading…