Hydrochloric Acid → 3-(4-methoxy-3-methylphenyl)propanoic acid

HRID 2220163Notes

Reaction equation

HRID 2220163 reaction equation
C(N(CC)CC)C.[CH3:8][O:9][C:10]1[CH:15]=[CH:14][C:13]([CH:16]=O)=[CH:12][C:11]=1[CH3:18].[CH3:19][C:20]1(C)[O:25]C(=O)CC(=O)[O:21]1.Cl>C(=O)([O-])[O-].[K+].[K+].O.C(O)=O>[CH3:8][O:9][C:10]1[CH:15]=[CH:14][C:13]([CH2:16][CH2:19][C:20]([OH:25])=[O:21])=[CH:12][C:11]=1[CH3:18]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 162492,2-Dimethyl-1,3-dioxane-4,6-dioneHCID 1229363-Methyl-4-anisaldehyde

Product 1

HCID 52376413-(4-methoxy-3-methylphenyl)propanoic acidYield 90.3%

Reagents, catalysts & solvents 3

HCID 284Formic AcidSolventHCID 962WaterSolvent2×HCID 11430Potassium CarbonateSolvent

Conditions

Temperature
60 °C

Procedure

Formic acid, 40.3 grams (0.88 mole), was stirred and cooled to below 5° C., to which was added 36.9 grams (0.37 mole) of triethylamine at a rate to maintain the reaction mixture temperature below 20° C. Upon completion of addition, 22.0 grams (0.15 mole) of (4-methoxy-3-methylphenyl)formaldehyde was added to the reaction mixture, followed by 22.2 grams (0.15 mole) of 2,2-dimethyl-1,3-dioxane-4,6-dione. Upon completion of addition, the reaction mixture was warmed to 60° C. where it stirred for about 15 minutes. The source of heat was removed, during a period when an exothermic reaction with evolution of gas took place within the reaction vessel. The heat source was returned once the exothermic reaction subsided, and heating of the reaction mixture was resumed for about two hours at 75° C. to 95° C. After this time the reaction mixture was cooled in an ice and water bath, and 200 mL of water, followed by 100 mL of aqueous 4N hydrochloric acid were added. The mixture was then extracted with two portions of diethyl ether. The combined extracts were washed with two portions of an aqueous dilute sodium chloride solution, with one portion of an aqueous saturated sodium chloride solution, and then dried with sodium sulfate. The mixture was filtered and the filtrate was concentrated under reduced pressure, yielding a residual solid. The solid was dissolved in an aqueous solution of 1N potassium carbonate and washed with two portions of diethyl ether. The aqueous layer was acidified with concentrated hydrochloric acid, and then it was extracted with two portions of diethyl ether. The combined ether extracts were washed with one portion of an aqueous dilute sodium chloride solution, and then dried with sodium sulfate. The mixture was filtered and concentrated under reduced pressure, yielding 26.3 grams of the subject compound. The NMR spectrum was consistent with the proposed structure.

Workup

  1. temperaturecooled to below 5° C., to which
  2. temperatureto maintain the reaction mixture temperature below 20° C
  3. additionwas added to the reaction mixture
  4. additionUpon completion of addition
  5. temperatureThe source of heat
  6. customwas removed, during a period when
  7. customan exothermic reaction with evolution of gas
  8. customthe exothermic reaction
  9. temperatureheating of the reaction mixture
  10. waitwas resumed for about two hours at 75° C. to 95° C
  11. additionwere added
  12. extractionThe mixture was then extracted with two portions of diethyl ether
  13. washThe combined extracts were washed with two portions of an aqueous dilute sodium chloride solution, with one portion of an aqueous saturated sodium chloride solution
  14. dry with materialdried with sodium sulfate
  15. filtrationThe mixture was filtered
  16. concentrationthe filtrate was concentrated under reduced pressure
  17. customyielding a residual solid
  18. washwashed with two portions of diethyl ether
  19. extractionit was extracted with two portions of diethyl ether
  20. washThe combined ether extracts were washed with one portion of an aqueous dilute sodium chloride solution
  21. dry with materialdried with sodium sulfate
  22. filtrationThe mixture was filtered
  23. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-b78ce119994640b5b23025f1f929393e
Source dataset
uspto-grants-2008_08
Patent number
US07417057B2

Reaction notes

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