Hexahydro-1,4-diazepine → Ammonia methanol

HRID 2230494Notes

Reaction equation

HRID 2230494 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>[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

6

Reactant 3

HCID 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 1049PyridineSolvent

Procedure

Alternately, combine 2-chloro-1-(2-ethoxyethyl)-1H-benzimidazole (15.56 g, 69.3 mmol) and [1,4]diazepane (13.89 g, 138.7 mmol), 1,8-diazabicyclo[5.4.0]undec-7-ene (12.34 mL, 83.1 minol), and pyridine (200 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 dichloromethane. Separate the layers and extract the aqueous layer two times with dichloromethane. Combine the organic layers, extract with aqueous 1 M sodium hydroxide solution, water, and then brine. Dry the organic layer over Na2SO4, filter, and evaporate in vacuo to give a residue. Chromatograph the residue on silica gel eluting with 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 dichloromethane
  5. customSeparate the layers
  6. extractionextract the aqueous layer two times with dichloromethane
  7. extractionextract with aqueous 1 M sodium hydroxide solution, water
  8. dry with materialDry the organic layer over Na2SO4
  9. filtrationfilter
  10. customevaporate in vacuo
  11. customto give a residue

Sources & evidence

ORD record
ord-ba2bfc5b9f6c485f87664ee12cd966ad
Source dataset
uspto-grants-2002_07
Patent number
US06423704B1

Reaction notes

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