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

HRID 59889

反応式

HRID 59889 の反応式
[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]

参加物

5

反応物 2

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

生成物 1

HCID 1183662723-(2-Ethoxyphenoxy)piperidine hydrochloride

試薬・触媒・溶媒 2

HCID 23948Rhodium触媒HCID 887Methanol溶媒

反応条件

温度
50 °C

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-6214c514af904a679fca40af421ffa92
出典データセット
uspto-grants-2016_09
特許番号
US09440949B2

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