Methylparaben → Methyl 4-(cyclopropylmethoxy)benzoate

HRID 1799247Notes

Reaction equation

HRID 1799247 reaction equation
C(=O)([O-])[O-].[K+].[K+].[OH:7][C:8]1[CH:17]=[CH:16][C:11]([C:12]([O:14][CH3:15])=[O:13])=[CH:10][CH:9]=1.[CH:18]1([CH2:21]Br)[CH2:20][CH2:19]1>[I-].[K+].CC(=O)CC>[CH:18]1([CH2:21][O:7][C:8]2[CH:9]=[CH:10][C:11]([C:12]([O:14][CH3:15])=[O:13])=[CH:16][CH:17]=2)[CH2:20][CH2:19]1

Participants

6

Reactant 3

HCID 7456MethylparabenHCID 11430Potassium CarbonateHCID 81503Bromomethylcyclopropane

Product 1

HCID 57589023Methyl 4-(cyclopropylmethoxy)benzoateYield 100.6%

Reagents, catalysts & solvents 2

HCID 4875Potassium IodideCatalystHCID 6569Methyl Ethyl KetoneSolvent

Conditions

Temperature
75 °C

Procedure

Potassium carbonate (114 g, 827 mmol) and potassium iodide (0.5 g) were added to a 2-butanone (535 mL) solution of methyl 4-hydroxybenzoate (52.4 g, 345 mmol) and cyclopropylmethyl bromide (72.7 g, 517 mmol) at room temperature. The mixture was stirred at 75° C. for 4 hours. The reaction solution was cooled to room temperature, and insoluble substances were separated by filtration. The insoluble substances were further washed with 2-butanone, and the filtrate was concentrated. The residue was dissolved in ethyl acetate (1 L), washed with water and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated, and the obtained residue was dried under reduced pressure to give 71.6 g of methyl 4-(cyclopropylmethoxy)benzoate (colorless crystal). All this crystal was dissolved in methanol (715 mL), and a 2 N sodium hydroxide aqueous solution (345 mL, 690 mmol) was added thereto. The resulting mixture was stirred at 60° C. for 3 hours, and the solvents (mainly methanol) were evaporated. The residue was suspended in water (500 mL), and 2 N hydrochloric acid (360 mL) was added thereto under ice-cooling with stirring. The precipitated white solid was collected by filtration, washed with water and n-hexane, and dried under reduced pressure to give 64.6 g of the title compound (white powder, yield: 97%).

Workup

  1. temperatureThe reaction solution was cooled to room temperature
  2. custominsoluble substances were separated by filtration
  3. washThe insoluble substances were further washed with 2-butanone
  4. concentrationthe filtrate was concentrated
  5. dissolutionThe residue was dissolved in ethyl acetate (1 L)
  6. washwashed with water and saturated brine
  7. dry with materialdried over anhydrous magnesium sulfate
  8. customThe solvent was evaporated
  9. customthe obtained residue was dried under reduced pressure

Sources & evidence

ORD record
ord-752b0651db764a7b8e8ee4c96956fe8d
Source dataset
uspto-grants-2013_01
Patent number
US08344029B2

Reaction notes

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