Hydrochloric Acid → Alosetron

HRID 484098Notes

Reaction equation

HRID 484098 reaction equation
[CH3:1][N:2]1[C:10]2[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=2[C:4]2[C:11](=[O:15])[NH:12][CH2:13][CH2:14][C:3]1=2.[H-].[Na+].Cl[CH2:19][C:20]1[N:21]=[CH:22][N:23](C(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[C:24]=1[CH3:25].Cl.[OH-].[Na+]>C(COC)OC.O>[NH3:2].[CH3:1][N:2]1[C:10]2[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=2[C:4]2[C:11](=[O:15])[N:12]([CH2:19][C:20]3[N:21]=[CH:22][NH:23][C:24]=3[CH3:25])[CH2:13][CH2:14][C:3]1=2

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 24758Sodium hydrideHCID 110469654-(Chloromethyl)-5-methyl-1-trityl-1H-imidazoleHCID 117902131H-Pyrido(4,3-b)indol-1-one, 2,3,4,5-tetrahydro-5-methyl-

Product 2

HCID 222AmmoniaHCID 2099AlosetronYield 119.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

A suspension of 2,3,4,5-tetrahydro-5-methyl-1H-pyrido[4,3-b]indol-1-one (400 mg) in dry dimethoxyethane (50 ml) was treated with sodium hydride (60% dispersion in oil; 100 mg), and the mixture was stirred at 60° under nitrogen for 6 h. 4-(Chloromethyl)-5-methyl-1-(triphenylmethyl)-1H-imidazole (474 mg) was added and the reaction mixture was stirred at 60° under nitrogen overnight. 2N Hydrochloric acid (10 ml) and water (10 ml) were then added, and the mixture was heated at reflux for 6 h. After cooling, the mixture was basified with 2N sodium hydroxide and the resulting mixture was extracted with ethyl acetate (2×50 ml). The combined, dried organic extracts were concentrated onto flash column chromatography (FCC) silica and purified by FCC eluting with dichloromethane:ethanol:0.88 ammonia (150:8:1) to give the title compound (352 mg) as a solid, t.l.c.

Workup

  1. stirringthe reaction mixture was stirred at 60° under nitrogen overnight
  2. temperaturethe mixture was heated
  3. temperatureat reflux for 6 h
  4. temperatureAfter cooling
  5. extractionthe resulting mixture was extracted with ethyl acetate (2×50 ml)
  6. concentrationdried organic extracts were concentrated onto flash column chromatography (FCC) silica
  7. custompurified by FCC
  8. washeluting with dichloromethane

Sources & evidence

ORD record
ord-2c68d00e567d4a0988ec0b64a8b4efce
Source dataset
uspto-grants-1993_07
Patent number
US05229407

Reaction notes

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