1-Bromo-3-chloropropane → 3-(3-Chloro-propoxy)-benzoic acid ethyl ester

HRID 410360Notes

Reaction equation

HRID 410360 reaction equation
[CH2:1]([O:3][C:4](=[O:12])[C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([OH:11])[CH:6]=1)[CH3:2].Br[CH2:14][CH2:15][CH2:16][Cl:17].C([O-])([O-])=O.[K+].[K+]>CC(C)=O>[CH2:1]([O:3][C:4](=[O:12])[C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([O:11][CH2:14][CH2:15][CH2:16][Cl:17])[CH:6]=1)[CH3:2]

Participants

5

Reactant 3

HCID 80061-Bromo-3-chloropropaneHCID 11430Potassium CarbonateHCID 24522Ethyl 3-hydroxybenzoate

Product 1

HCID 540513773-(3-Chloro-propoxy)-benzoic acid ethyl esterYield 68.7%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

To a solution of ethyl-3-hydroxybenzoate (5.0 g, 30 mmol) in acetone (250 ml) at rt was added 1-bromo-3-chloro-propane (5.67 g, 36 mmol) and K2CO3 (12.4 g, 90 mmol). The resulting suspension was heated to reflux where it was maintained for 25 h. After this time, the mixture was concentrated under reduced pressure and the resulting solid was partitioned between H2O and EtOAc. The organic phase was separated and the aqueous phase was extracted with additional EtOAc. The combined organic fractions were washed with 1N HCl and brine, dried (Na2SO4), filtered and concentrated under reduced pressure to provide the crude product. Purification by chromatography on silica eluting with 5% EtOAc/hexane gave 3-(3-chloro-propoxy)-benzoic acid ethyl ester as a colourless oil (5.0 g, 68%).

Workup

  1. temperatureThe resulting suspension was heated
  2. temperatureto reflux where it
  3. temperaturewas maintained for 25 h
  4. concentrationAfter this time, the mixture was concentrated under reduced pressure
  5. customthe resulting solid was partitioned between H2O and EtOAc
  6. customThe organic phase was separated
  7. extractionthe aqueous phase was extracted with additional EtOAc
  8. washThe combined organic fractions were washed with 1N HCl and brine
  9. dry with materialdried (Na2SO4)
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure
  12. customto provide the crude product
  13. customPurification by chromatography on silica eluting with 5% EtOAc/hexane

Sources & evidence

ORD record
ord-3acf2a8cfe82465ca183799ca49e61c2
Source dataset
uspto-grants-2014_06
Patent number
US08759520B2

Reaction notes

Loading…