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

HRID 1744006Notes

Reaction equation

HRID 1744006 reaction equation
C(OCCCCC)(=O)C.[OH:10][C:11]1[CH:20]=[CH:19][C:14]([C:15]([O:17]C)=[O:16])=[CH:13][CH:12]=1.C(=O)([O-])[O-].[K+].[K+].Cl.[Cl:28][CH2:29][CH2:30][N:31]1[CH2:36][CH2:35][CH2:34][CH2:33][CH2:32]1>>[ClH:28].[N:31]1([CH2:30][CH2:29][O:10][C:11]2[CH:20]=[CH:19][C:14]([C:15]([OH:17])=[O:16])=[CH:13][CH:12]=2)[CH2:36][CH2:35][CH2:34][CH2:33][CH2:32]1

Participants

5

Reactant 4

HCID 7456MethylparabenHCID 11430Potassium CarbonateHCID 12348Amyl AcetateHCID 74826Piperidine, 1-(2-chloroethyl)-, hydrochloride

Product 1

HCID 57438354-(2-Piperidinoethoxy)benzoic acid hydrochlorideYield 91%

Procedure

To a 2000 gallon reaction tank were added: 1320L of amyl acetate, 167.42 kg of methyl 4-hydroxybenzoate, 408.6 kg of anhydrous potassium carbonate, and 283.5 kg of β-chloroethylpiperidine hydrochloride. The mixture was heated to 120° C.–125° C. for 5 hours, at which time HPLC analysis indicated complete consumption of the methyl 4-hydroxybenzoate. The tank was cooled to less than 50° C. 880L of deionized water were added to the tank. The layers were separated and the aqueous layer was discarded. In a glass-lined tank was mixed 367 liters of food grade hydrochloric acid and 184L of deionized water. The acid mixture was combined with the organic layer. The layers were separated and the organic layer was discarded. The mixture of the intermediate ester in aqueous acid heated to reflux until HPLC suggested no further consumption of the ester (13 hours). The mixture was cooled to less than 40° C., 550 liters of acetone was added to the mixture and the mixture was cooled to 0° C.–5° C. and stirred for 1 hour. The product was collected by filtration on a centrifuge. The wet cake was rinsed on the centrifuge with 400L of acetone. The product was dried in a rotary vacuum (double cone) dryer at less than 50° C. and 25–27 inches in mercury. Yield was 91% of theoretical.

Workup

  1. customTo a 2000 gallon reaction tank
  2. additionwere added
  3. temperatureThe mixture was heated to 120° C.–125° C. for 5 hours, at which time HPLC analysis
  4. customconsumption of the methyl 4-hydroxybenzoate
  5. temperatureThe tank was cooled to less than 50° C
  6. addition880L of deionized water were added to the tank
  7. customThe layers were separated
  8. additionIn a glass-lined tank was mixed 367 liters of food grade hydrochloric acid and 184L of deionized water
  9. customThe layers were separated
  10. additionThe mixture of the intermediate ester in aqueous acid
  11. temperatureheated
  12. temperatureto reflux until HPLC
  13. customno further consumption of the ester (13 hours)
  14. temperatureThe mixture was cooled to less than 40° C.
  15. addition550 liters of acetone was added to the mixture
  16. temperaturethe mixture was cooled to 0° C.–5° C.
  17. filtrationThe product was collected by filtration on a centrifuge
  18. washThe wet cake was rinsed on the centrifuge with 400L of acetone
  19. customThe product was dried in a rotary vacuum (double cone) dryer at less than 50° C.

Sources & evidence

ORD record
ord-589e9235e8ff4ca0b7827fb05f9bc183
Source dataset
uspto-grants-2006_03
Patent number
US07012153B2

Reaction notes

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