Potassium Hydroxide → Emedastine EP Impurity E

HRID 637018Notes

Reaction equation

HRID 637018 reaction equation
C(OC([N:6]1[CH2:12][CH2:11][CH2:10][N:9]([C:13]2[N:17]([CH2:18][CH2:19][O:20][CH2:21][CH3:22])[C:16]3[CH:23]=[CH:24][CH:25]=[CH:26][C:15]=3[N:14]=2)[CH2:8][CH2:7]1)=O)C.O.NN.[OH-].[K+]>C(O)CO.O>[CH2:21]([O:20][CH2:19][CH2:18][N:17]1[C:16]2[CH:23]=[CH:24][CH:25]=[CH:26][C:15]=2[N:14]=[C:13]1[N:9]1[CH2:10][CH2:11][CH2:12][NH:6][CH2:7][CH2:8]1)[CH3:22]

Participants

6

Reactant 3

HCID 14797Potassium HydroxideHCID 24654Hydrazine hydrate (1:1)HCID 143561191-ethoxycarbonyl-4-(1-(2-ethoxyethyl)-1H-benzimidazol-2-yl)[1,4]diazepane

Product 1

HCID 9984168Emedastine EP Impurity E

Reagents, catalysts & solvents 2

HCID 174Ethylene GlycolSolventHCID 962WaterSolvent

Procedure

Combine 1-ethoxycarbonyl-4-(1-(2-ethoxyethyl)-1H-benzimidazol-2-yl)[1,4]diazepane (17.2 g, 47.6 mmol), hydrazine hydrate (40 mL), and potassium hydroxide (40.7 g, 725 mmol) in ethylene glycol (150 mL). Heat to reflux. After 5 hours, cool the reaction mixture and dilute with water (500 mL). Extract three times with dichloromethane. Combine the dichloromethane layers and extract with a saturated aqueous sodium bicarbonate solution and then brine. Dry the organic layer over MgSO4, filter, and evaporate in vacuo to give the title compound: Rf=0.25 (silica gel, dichloromethane/methanol, 90/10).

Workup

  1. temperatureHeat to reflux
  2. temperaturecool the reaction mixture
  3. extractionExtract three times with dichloromethane
  4. extractionextract with a saturated aqueous sodium bicarbonate solution
  5. dry with materialDry the organic layer over MgSO4
  6. filtrationfilter
  7. customevaporate in vacuo

Sources & evidence

ORD record
ord-dc8e2eb74b44444585e49798ae338f5f
Source dataset
uspto-grants-2001_02
Patent number
US06194406B1

Reaction notes

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