Pyridine → Ammonia methanol

HRID 1584423Notes

Reaction equation

HRID 1584423 reaction equation
Cl[C:2]1[N:6]([CH2:7][CH2:8][O:9][CH2:10][CH3:11])[C:5]2[CH:12]=[CH:13][CH:14]=[CH:15][C:4]=2[N:3]=1.[NH:16]1[CH2:22][CH2:21][CH2:20][NH:19][CH2:18][CH2:17]1.N12CCCN=C1CCCCC2.N1C=CC=CC=1>CO.C(OCC)(=O)C>[NH3:3].[CH3:8][OH:9].[CH2:10]([O:9][CH2:8][CH2:7][N:6]1[C:5]2[CH:12]=[CH:13][CH:14]=[CH:15][C:4]=2[N:3]=[C:2]1[N:16]1[CH2:22][CH2:21][CH2:20][NH:19][CH2:18][CH2:17]1)[CH3:11]

Participants

7

Reactant 4

HCID 1049PyridineHCID 68163Hexahydro-1,4-diazepineHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 104893562-chloro-1-(2-ethoxyethyl)-1H-benzimidazole

Product 2

HCID 9984168Emedastine EP Impurity EHCID 21705897Ammonia methanolYield 2%

Reagents, catalysts & solvents 1

HCID 21584119Ethylacetate methanolSolvent

Procedure

Combine 2-chloro-1-(2-ethoxyethyl)-1H-benzimidazole (12.2 g, 54.2 mmol) and [1,4]diazepane (11.34 g, 113 mmol), 1,8-diazabicyclo[5.4.0]undec-7-ene (9 mL), and pyridine (90 mL). Heat to reflux. After 18 hours, cool to ambient temperature and evaporate in vacuo to give a residue. Partition the residue between aqueous 1 M sodium hydroxide solution and ethyl acetate. Separate the layers and extract the aqueous layer two times with ethyl acetate. Combine the organic layers, dry over Na2SO4, filter, and evaporate in vacuo to give a residue. Chromatograph the residue on silica gel eluting sequentially with 30% methanol/ethyl acetate and then 2% concentrated aqueous ammonia/methanol to give the title compound: Rf =0.26 (silica gel, 2% concentrated aqueous ammonia/methanol).

Workup

  1. temperatureHeat to reflux
  2. customevaporate in vacuo
  3. customto give a residue
  4. customPartition the residue between aqueous 1 M sodium hydroxide solution and ethyl acetate
  5. customSeparate the layers
  6. extractionextract the aqueous layer two times with ethyl acetate
  7. dry with materialdry over Na2SO4
  8. filtrationfilter
  9. customevaporate in vacuo
  10. customto give a residue

Sources & evidence

ORD record
ord-b2437ae751434e02b555820446ecf2ab
Source dataset
uspto-grants-1999_08
Patent number
US05932571

Reaction notes

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