Methylparaben → 4-(2-Piperidinoethoxy)benzoic acid hydrochloride

HRID 1780955Notes

Reaction equation

HRID 1780955 reaction equation
[OH:1][C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8]C)=[O:7])=[CH:4][CH:3]=1.Cl.[Cl:13][CH2:14][CH2:15][N:16]1[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]1.C(=O)([O-])[O-].[K+].[K+].C(OCC)(=O)C>O>[ClH:13].[N:16]1([CH2:15][CH2:14][O:1][C:2]2[CH:11]=[CH:10][C:5]([C:6]([OH:8])=[O:7])=[CH:4][CH:3]=2)[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]1

Participants

6

Reactant 4

HCID 7456MethylparabenHCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 74826Piperidine, 1-(2-chloroethyl)-, hydrochloride

Product 1

HCID 57438354-(2-Piperidinoethoxy)benzoic acid hydrochloride

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a 250 mL 3 neck flask with mechanical stirring and condenser, and a heating apparatus consisting of an RTD probe in the flask hooked via a temperature controller to a heating mantle and under nitrogen atmosphere, the following was added: 7.61 g of methyl 4-hydroxybenzoate, 11.05 g of β-chloroethylpiperidine hydrochloride, 16.59 g of powdered potassium carbonate and 60 mL of ethyl acetate. The mixture was heated slowly to reflux. After overnight reflux, the mixture was cooled to ambient temperature, after which 60 mL of deionized water was added. The aqueous layer was separated and discarded. The organic layer was extracted with 4N hydrochloride (3 aliquots of 20 mL). The combined acid extracts were heated to reflux. After 1 hour at reflux, HPLC indicated the saponification to be 60% complete. After 4 hours, the reaction was near 100% complete. The mixture was cooled to 0° C.-5° C. and stirred. The resulting crystals were filtered, rinsed with acetone and dried.

Workup

  1. customcondenser, and a heating apparatus consisting of an RTD probe in the flask
  2. additionthe following was added
  3. temperatureThe mixture was heated slowly
  4. temperatureto reflux
  5. temperatureAfter overnight reflux
  6. customThe aqueous layer was separated
  7. extractionThe organic layer was extracted with 4N hydrochloride (3 aliquots of 20 mL)
  8. temperatureThe combined acid extracts were heated to reflux
  9. temperatureAfter 1 hour at reflux
  10. temperatureThe mixture was cooled to 0° C.-5° C.
  11. filtrationThe resulting crystals were filtered
  12. washrinsed with acetone
  13. customdried

Sources & evidence

ORD record
ord-eb82cfb403a14a159e26a2010c1cf21e
Source dataset
uspto-grants-1997_05
Patent number
US05631369

Reaction notes

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