Triethylamine → Emedastine

HRID 637016Notes

Reaction equation

HRID 637016 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.[CH3:16][N:17]1[CH2:23][CH2:22][CH2:21][NH:20][CH2:19][CH2:18]1.C(N(CC)CC)C.C(OCC)(=O)C.CCCCCC>CO.ClCCl>[CH3:16][N:17]1[CH2:23][CH2:22][CH2:21][N:20]([C:2]2[N:6]([CH2:7][CH2:8][O:9][CH2:10][CH3:11])[C:5]3[CH:12]=[CH:13][CH:14]=[CH:15][C:4]=3[N:3]=2)[CH2:19][CH2:18]1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 2283491-Methylhomopiperazine2×HCID 104893562-chloro-1-(2-ethoxyethyl)-1H-benzimidazoleHCID 21226206Ethyl acetate hexane

Product 1

HCID 3219Emedastine

Reagents, catalysts & solvents 1

HCID 21226129Dichloromethane methanolSolvent

Conditions

Temperature
70 °C

Procedure

Combine 2-chloro-1-(2-ethoxyethyl)-1H-benzimidazole (22.3 g, 99.4 mmol), 1-methyl[1,4]diazepane (19 mL, 152.8 mmol), and triethylamine (75 mL). Heat to 70° C. After 18 hours, add 1-methyl[1,4]diazepane (10 mL) and continue to heat at reflux. After 96 hours, cool to ambient temperature and partition the reaction mixture between water and ethyl acetate. Separate the layers and extract the organic layer with a saturated aqueous sodium bicarbonate solution and then brine. Dry the organic layer over MgSO4, filter, and evaporate in vacuo to give a residue. Chromatograph the residue on silica gel eluting sequentially with 50% ethyl acetate/hexane and then 10% methanol/dichloromethane to give 1-methyl-4-(1-(2-ethoxyethyl)-1H-benzimidazol-2-yl)[1,4]diazepane: Rf=0.52 (silica gel, dichloromethane/methanol/concentrated aqueous ammonia, 90/10/0.1).

Workup

  1. temperatureto heat
  2. temperatureat reflux
  3. waitAfter 96 hours
  4. temperaturecool to ambient temperature
  5. custompartition the reaction mixture between water and ethyl acetate
  6. customSeparate the layers
  7. extractionextract the organic layer with a saturated aqueous sodium bicarbonate solution
  8. dry with materialDry the organic layer over MgSO4
  9. filtrationfilter
  10. customevaporate in vacuo
  11. customto give a residue

Sources & evidence

ORD record
ord-9a4d5baae8064d5aac0a7606d59f1d28
Source dataset
uspto-grants-2001_02
Patent number
US06194406B1

Reaction notes

Loading…