Hydrochloric Acid → 3-(2-Ethoxyphenoxy)piperidine hydrochloride

HRID 59889

Reaction equation

HRID 59889 reaction equation
[ClH:1].[CH2:2]([O:4][C:5]1[CH:17]=[CH:16][CH:15]=[CH:14][C:6]=1[O:7][C:8]1[CH:9]=[N:10][CH:11]=[CH:12][CH:13]=1)[CH3:3]>[Rh].CO>[ClH:1].[CH2:2]([O:4][C:5]1[CH:17]=[CH:16][CH:15]=[CH:14][C:6]=1[O:7][CH:8]1[CH2:13][CH2:12][CH2:11][NH:10][CH2:9]1)[CH3:3]

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 126734873-(2-Ethoxyphenoxy)pyridine

Product 1

HCID 1183662723-(2-Ethoxyphenoxy)piperidine hydrochloride

Reagents, catalysts & solvents 2

HCID 23948RhodiumCatalystHCID 887MethanolSolvent

Conditions

Temperature
50 °C

Procedure

Aqueous 12.2M hydrochloric acid solution (80.0 mL, 0.976 mol) was added slowly to a mixture of 3-(2-ethoxyphenoxy)pyridine (210 g, 0.976 mol), rhodium (5% on alumina, 21 g, 0.010 mol), and methanol (2.1 L) in a Parr reactor. The reactor was purged sequentially with nitrogen and hydrogen (4 times each), and then was heated to 50° C. and pressurized to 50 psi with hydrogen. After 9 hours, the reactor was cooled to 25° C. and was purged with nitrogen. The catalyst was removed by filtration, rinsing with methanol. The resulting methanol solution was distilled to a low volume under reduced pressure at 50-55° C.; ethyl acetate (2.3 L) was added and the distillation was continued at ambient pressure and at constant volume with the addition of further ethyl acetate (1.5 L). The distillation was stopped when the solution became turbid. The mixture was cooled to 20° C. and the resulting crystals were collected by filtration, rinsing with ethyl acetate (0.70 L), to afford after drying 3-(2-ethoxyphenoxy)piperidine hydrochloride (201 g). 1H NMR (400 MHz, DMSO-d6) δ 9.20 (br s, 2H), 7.12 (d, 1H), 7.03 (m, 2H), 6.89 (m, 1H), 4.45 (m, 1H), 4.04 (q, 2H), 3.27 (app dd, 1H), 3.05 (m, 3H), 1.94 (m, 2H), 1.72 (m, 2H), 1.35 (t, 3H). MS (ES+) 222.1 (M+H).

Workup

  1. customThe reactor was purged sequentially with nitrogen and hydrogen (4 times each), and
  2. temperaturethe reactor was cooled to 25° C.
  3. customwas purged with nitrogen
  4. customThe catalyst was removed by filtration
  5. washrinsing with methanol
  6. distillationThe resulting methanol solution was distilled to a low volume under reduced pressure at 50-55° C.
  7. additionethyl acetate (2.3 L) was added
  8. distillationthe distillation
  9. additionwas continued at ambient pressure and at constant volume with the addition of further ethyl acetate (1.5 L)
  10. distillationThe distillation
  11. temperatureThe mixture was cooled to 20° C.
  12. filtrationthe resulting crystals were collected by filtration
  13. washrinsing with ethyl acetate (0.70 L)
  14. customto afford
  15. dry with materialafter drying 3-(2-ethoxyphenoxy)piperidine hydrochloride (201 g)

Sources & evidence

ORD record
ord-6214c514af904a679fca40af421ffa92
Source dataset
uspto-grants-2016_09
Patent number
US09440949B2

Linked notes

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