Hydrochloric Acid → N-(4-{2-[4-hydroxy-4-(4-methyl-benzyl)-piperidin-1-yl]-ethoxy}-phenyl)-methanesulfonamide hydrochloride

HRID 1419893Notes

Reaction equation

HRID 1419893 reaction equation
[CH3:1][C:2]1[CH:15]=[CH:14][C:5]([CH2:6][C:7]2([OH:13])[CH2:12][CH2:11][NH:10][CH2:9][CH2:8]2)=[CH:4][CH:3]=1.Br[CH2:17][CH2:18][O:19][C:20]1[CH:25]=[CH:24][C:23]([NH:26][S:27]([CH3:30])(=[O:29])=[O:28])=[CH:22][CH:21]=1.C(=O)([O-])[O-].[K+].[K+].[ClH:37]>CC(=O)CC.C(O)C.C(OCC)(=O)C.O>[ClH:37].[OH:13][C:7]1([CH2:6][C:5]2[CH:4]=[CH:3][C:2]([CH3:1])=[CH:15][CH:14]=2)[CH2:8][CH2:9][N:10]([CH2:17][CH2:18][O:19][C:20]2[CH:21]=[CH:22][C:23]([NH:26][S:27]([CH3:30])(=[O:28])=[O:29])=[CH:24][CH:25]=2)[CH2:11][CH2:12]1

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 105362424-(4-Methylbenzyl)-piperidin-4-olHCID 111091562-(4-Methanesulfonamidophenoxy)ethyl bromide

Product 1

HCID 70046177N-(4-{2-[4-hydroxy-4-(4-methyl-benzyl)-piperidin-1-yl]-ethoxy}-phenyl)-methanesulfonamide hydrochlorideYield 41%

Reagents, catalysts & solvents 4

HCID 702EthanolSolventHCID 962WaterSolventHCID 6569Methyl Ethyl KetoneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 4-(4-methyl-benzyl)-piperidin-4-ol (0.35 g, 1.7 mmol), N-[4-(2-bromethoxy)-phenyl]-methansulfonamide (0.5 g, 1.7 mmol) and potassium carbonate (0.25 g, 1.8 mmol) in 2-butanone (20 ml) was refluxed overnight. It was cooled to room temperature, 30 ml of H2O were added and the organic phase was separated. The water phase was extracted two times with ethyl acetate. The organic phases were then pooled, dried with Na2SO4 and the solvent evaporated. The residue was chromatographed over silica gel (CH2Cl2 --MeOH, 95:5) to give a yellowish foam which was dissolved in ethanol (5 ml) and ethyl acetate (10 ml). 1.1 Equivalent of ethanolic HCl were added to give N-(4-{2-[4-hydroxy-4-(4-methyl-benzyl)-piperidin-1-yl]-ethoxy}-phenyl)-methanesulfonamide hydrochloride (0.32 g, 41%) as colorless solid, m.p. >75°-78° C. dec. and MS: m/e=419.5 (M+H+).

Workup

  1. temperaturewas refluxed overnight
  2. customthe organic phase was separated
  3. extractionThe water phase was extracted two times with ethyl acetate
  4. dry with materialdried with Na2SO4
  5. customthe solvent evaporated
  6. customThe residue was chromatographed over silica gel (CH2Cl2 --MeOH, 95:5)
  7. customto give a yellowish foam which

Sources & evidence

ORD record
ord-63ecbd54fdde44a2a7858c95ab5b4b3e
Source dataset
uspto-grants-1999_03
Patent number
US05889026

Reaction notes

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