Hydrogen Bromide → 2-{2-[4-(2-Dimethylaminoethyl)piperidino]ethoxy}phenol dihydrochloride

HRID 962447Notes

Reaction equation

HRID 962447 reaction equation
C[O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[O:9][CH2:10][CH2:11]Br.[ClH:13].Cl.[CH3:15][N:16]([CH3:25])[CH2:17][CH2:18][CH:19]1[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]1.[OH-].[Na+].Br.Cl>CCOCC.C(O)(=O)C.CN(C=O)C.C(N(CC)CC)C>[ClH:13].[ClH:13].[CH3:25][N:16]([CH3:15])[CH2:17][CH2:18][CH:19]1[CH2:24][CH2:23][N:22]([CH2:11][CH2:10][O:9][C:4]2[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=2[OH:2])[CH2:21][CH2:20]1

Participants

10

Reactant 5

HCID 260Hydrogen BromideHCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 17990992-(2-Bromoethoxy)anisoleHCID 19085438N,N-Dimethyl-2-(piperidin-4-yl)ethanamine dihydrochloride

Product 1

HCID 190854062-{2-[4-(2-Dimethylaminoethyl)piperidino]ethoxy}phenol dihydrochloride

Reagents, catalysts & solvents 4

HCID 176Acetic AcidSolventHCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

A mixture of 2-bromoethyl 2-methoxyphenyl ether (7.5 g), 4-(2-dimethylaminoethyl)piperidine dihydrochloride (7.44 g), triethylamine (18.1 ml) and DMF (50 ml) was heated on a steam bath for 18 hours. The mixture was poured into ice/water (500 ml) and basified with 2M sodium hydroxide. The product was extracted into dichloromethane to give an oil. The oil was triturated with ether. The ether was decanted off and evaporated to give crude 4-(2-dimethylaminoethyl)-1-[2-(2-methoxyphenoxy)ethyl]piperidine (4.58 g) which was added to glacial acetic acid (17 ml) and 48% hydrobromic acid (57 ml). The mixture was heated on a steam bath for 4 hours and then evaporated to dryness. The residue was dissolved in water, basified with 2M sodium hydroxide solution and extracted with dichloromethane to give an oil. The oil was dissolved in ether and acidified with ethereal hydrogen chloride The precipitate was collected by filtration and recrystallised from propan-2-ol to give 2-{2-[4-(2-dimethylaminoethyl)piperidino]ethoxy}phenol dihydrochloride m.p. 273°-275° C.

Workup

  1. temperaturewas heated on a steam bath for 18 hours
  2. extractionThe product was extracted into dichloromethane
  3. customto give an oil
  4. customThe oil was triturated with ether
  5. customThe ether was decanted off
  6. customevaporated
  7. customto give crude 4-(2-dimethylaminoethyl)-1-[2-(2-methoxyphenoxy)ethyl]piperidine (4.58 g) which
  8. temperatureThe mixture was heated on a steam bath for 4 hours
  9. customevaporated to dryness
  10. dissolutionThe residue was dissolved in water
  11. extractionextracted with dichloromethane
  12. customto give an oil
  13. filtrationwas collected by filtration
  14. customrecrystallised from propan-2-ol

Sources & evidence

ORD record
ord-788468f7490b467985682893098f7c02
Source dataset
uspto-grants-1998_06
Patent number
US05760035

Reaction notes

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