Acetic Acid → 4-(4-Hydroxyphenyl)butanoic acid

HRID 968830Notes

Reaction equation

HRID 968830 reaction equation
C[O:2][C:3]1[CH:8]=[CH:7][C:6]([CH2:9][CH2:10][CH2:11][C:12]([OH:14])=[O:13])=[CH:5][CH:4]=1.Cl.N1C=CC=CC=1.C(O)(=O)C.Cl>COC(C)(C)C.O>[OH:2][C:3]1[CH:4]=[CH:5][C:6]([CH2:9][CH2:10][CH2:11][C:12]([OH:14])=[O:13])=[CH:7][CH:8]=1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 313Hydrochloric AcidHCID 782804-(4-Methoxyphenyl)butyric acidHCID 10176127Pyridinium chloride

Product 1

HCID 2799834-(4-Hydroxyphenyl)butanoic acidYield 96.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 15413tert-Butyl methyl etherSolvent

Conditions

Temperature
190 °C

Procedure

A 22-L 4-necked round bottom flask was equipped with a condenser, nitrogen inlet, thermometer lead and overhead stirring apparatus. The flask was charged with 4-(4-methoxyphenyl)butyric acid (2250 g, 11.58 moles) followed by pyridine hydrochloride (5360 g, 46.34 moles, 4 eq). The resulting mixture of the two solids was heated under nitrogen to 185-195° C., with stirring commencing by 50° C. The flask contents were held at 185-195° C., and reaction progress was monitored by TLC (50/50 v/v hexanes/ethyl acetate+1% v/v acetic acid, panisaldehyde stain for visualization). After two hours, TLC analysis indicated complete consumption of starting material. The heat source was removed and the mixture allowed to cool to 90° C., after which 5N HCl (2900 mL, 14.47 moles, 1.25 eq) and H2O (2700 mL) were added sequentially. Stirring was continued until the pot temperature reached 35° C. The mixture was transferred to a 22-L bottom-outlet flask and diluted with t-butyl methyl ether (MTBE, 6000 mL). The layers were separated and the aqueous portion was reextracted with MTBE (3×4000 mL). The organic portions were combined and back-washed with 5N HCl (750 mL). After drying (Na2SO4) and filtration, the solution was concentrated in vacuo to afford the title compound as a white solid (2020 g, 96.7%). 1H NMR (500 MHz, DMSO-d6) δ 1.70 (m, 2H), 2.15 (t, 2H), 2.45 (t, 2H), 3.33 (s, 1H), 6.65 (d, 2H), 6.95 (d, 2H). 13C NMR (DMSO-d6) δ 26.5, 32.5, 33.5, 114.6, 129.0, 131.2, 155.3, 174.2.

Workup

  1. customA 22-L 4-necked round bottom flask was equipped with a condenser, nitrogen inlet
  2. additionThe resulting mixture of the two solids
  3. stirringwith stirring commencing by 50° C
  4. customwere held at 185-195° C.
  5. customreaction progress
  6. customconsumption of starting material
  7. customThe heat source was removed
  8. temperatureto cool to 90° C.
  9. stirringStirring
  10. customreached 35° C
  11. customThe mixture was transferred to a 22-L bottom-outlet flask
  12. customThe layers were separated
  13. washback-washed with 5N HCl (750 mL)
  14. customAfter drying
  15. filtration(Na2SO4) and filtration
  16. concentrationthe solution was concentrated in vacuo

Sources & evidence

ORD record
ord-fe1719e856ec4323a95b4679d63f4fac
Source dataset
uspto-grants-2007_12
Patent number
US07304062B2

Reaction notes

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