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

HRID 1780957Notes

Reaction equation

HRID 1780957 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.C(=O)([O-])[O-].[K+].[K+].Cl.[Cl:19][CH2:20][CH2:21][N:22]1[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]1>C(OCCCCC)(=O)C>[ClH:19].[N:22]1([CH2:21][CH2:20][O:1][C:2]2[CH:11]=[CH:10][C:5]([C:6]([OH:8])=[O:7])=[CH:4][CH:3]=2)[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]1

Participants

5

Reactant 3

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 12348Amyl AcetateSolvent

Procedure

To a 2000 gallon tank were added: 1320 L of amyl acetate, 167.42 kg of methyl 4-hydroxybenzoate, 408.6 kg of 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. 880 L 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 L of food grade hydrochloric acid and 184 L 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 L 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 400 L 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. additionTo a 2000 gallon tank were added
  2. temperatureThe mixture was heated to 120° C.-125° C. for 5 hours, at which time HPLC analysis
  3. customconsumption of the methyl 4-hydroxybenzoate
  4. temperatureThe tank was cooled to less than 50° C
  5. addition880 L of deionized water were added to the tank
  6. customThe layers were separated
  7. additionwas mixed 367 L of food grade hydrochloric acid and 184 L of deionized water
  8. customThe layers were separated
  9. additionThe mixture of the intermediate ester in aqueous acid
  10. temperatureheated
  11. temperatureto reflux until HPLC
  12. customno further consumption of the ester (13 hours)
  13. temperatureThe mixture was cooled to less than 40° C
  14. addition550 L of acetone was added to the mixture
  15. temperaturethe mixture was cooled to 0° C.-5° C.
  16. filtrationThe product was collected by filtration on a centrifuge
  17. washThe wet cake was rinsed on the centrifuge with 400 L of acetone
  18. customThe product was dried in a rotary vacuum (double cone) dryer at less than 50° C.

Sources & evidence

ORD record
ord-b190f2bf04fc450e98f6452e9e676dfb
Source dataset
uspto-grants-1997_05
Patent number
US05631369

Reaction notes

Loading…