Hydrochloric Acid → 5-(2-Chlorophenoxy)pentanoic acid

HRID 341354Notes

Reaction equation

HRID 341354 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[OH:8].Br[CH2:10][CH2:11][CH2:12][CH2:13][C:14]([O:16]CC)=[O:15].C(=O)([O-])[O-].[K+].[K+].[OH-].[Na+].Cl>CC(=O)CC>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[O:8][CH2:10][CH2:11][CH2:12][CH2:13][C:14]([OH:16])=[O:15]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 72452-ChlorophenolHCID 11430Potassium CarbonateHCID 14798Sodium HydroxideHCID 84580Ethyl 5-bromovalerate

Product 1

HCID 289716405-(2-Chlorophenoxy)pentanoic acidYield 97%

Reagents, catalysts & solvents 1

HCID 6569Methyl Ethyl KetoneSolvent

Conditions

Temperature
25 °C

Procedure

A 500 ml 3-neck round bottom flask equipped with a magnetic stirrer bar and a reflux condenser was charged with 12.86 (100 mmol) 2-chloro phenol, 23.49 g (110 mmol) ethyl 5-bromovalerate, 16.60 g (120 mmol) potassium carbonate and 300 mL of 2-butanone. The slurry heated to reflux. After stirring for 20 hr at reflux (completeness confirmed by HPLC), the reaction mixture was cooled to 25° C., filtered and concentrated. The residue was taken up in of water (300 ml) and treated with 100 ml (200 mmol) 2N aqueous sodium hydroxide. This suspension was heated to reflux for 2 hours until it turned to a solution. The solution was cooled to 25° C. Ice was added to further cool to 0° C. The yellow solution was acidified with aqueous 105 ml 2N hydrochloric acid. The resulting white solid was isolated by filtration washing with water twice then hexanes twice to yield 22.24 g (97%) of the desired product, Mp 71-72° C. Combustion analysis: Found: C, 57.66%; H, 5.82%, Cl, 15.5%; Calculated: C, 57.78%; H, 5.73%; Cl, 15.5%; 1H NMR (d6-DMSO): δ 12.1, broad s, 1H (COOH); δ 7.40, dd, 1H (aryl H); δ 7.25, m, 1H (aryl H); δ 7.10, dd, 1H (aryl H); δ 6.9, m, 1H (aryl A); δ 4.0, t, 2H (CH2 α ArO); δ 2.3, t, 2H (CH2 α COOH); δ 1.7, m, 4H (rest of CH2's).

Workup

  1. customA 500 ml 3-neck round bottom flask equipped with a magnetic stirrer bar and a reflux condenser
  2. temperatureThe slurry heated to reflux
  3. temperatureat reflux (completeness confirmed by HPLC)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. temperatureThis suspension was heated
  7. temperatureto reflux for 2 hours until it
  8. temperatureThe solution was cooled to 25° C
  9. additionIce was added
  10. temperatureto further cool to 0° C
  11. customThe resulting white solid was isolated by filtration
  12. washwashing with water twice

Sources & evidence

ORD record
ord-1621e3d8a249476cab44e1502effbdf2
Source dataset
uspto-grants-2014_11
Patent number
US08895777B2

Reaction notes

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