Hydrochloric Acid → Alosetron

HRID 2379159Notes

Reaction equation

HRID 2379159 reaction equation
[CH3:1][C:2]1[N:6](C(OCC2C=CC=CC=2)=O)[CH:5]=[N:4][C:3]=1[CH2:17][N:18]1[CH2:31][CH2:30][C:21]2[N:22]([CH3:29])[C:23]3[CH:24]=[CH:25][CH:26]=[CH:27][C:28]=3[C:20]=2[C:19]1=[O:32].C(O)C.Cl>CO>[CH3:29][N:22]1[C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][C:28]=2[C:20]2[C:19](=[O:32])[N:18]([CH2:17][C:3]3[N:4]=[CH:5][NH:6][C:2]=3[CH3:1])[CH2:31][CH2:30][C:21]1=2

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 702EthanolHCID 18957736Phenylmethyl 5-methyl-4-[(2,3,4,5-tetrahydro-5-methyl-1-oxo-1H-pyrido[4,3-b]indol-2yl)methyl]-1H-imidazole-1-carboxylate

Product 1

HCID 2099AlosetronYield 75%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of phenylmethyl 5-methyl-4-[(2,3,4,5-tetrahydro-5-methyl-1-oxo-1H-pyrido[4,3-b]indol-2-yl)methyl]-1H-imidazole-1-carboxylate (134 mg) in a mixture of absolute ethanol and 2N hydrochloric acid (2:1; 30 ml) was heated on a steam bath for 15 min. After cooling, the solution was concentrated in vacuo to ca. 20 ml and diluted with water (40 ml). The mixture was then washed with ethyl acetate (2×40 ml) and the acidic aqueous layer was basified with potassium carbonate solution. The solution was then extracted with ethyl acetate (3×50 ml) and the combined, dried organic extracts, were concentrated onto FCC silica and purified by FCC eluting with System A (150:8:1) to give a solid. This was dissolved in hot methanol and triturated with ether to give the title compound (69 mg). The 1H-n.m.r. and t.l.c. data obtained for this material were consistent with those obtained for the product of Example 20.

Workup

  1. temperaturewas heated on a steam bath for 15 min
  2. temperatureAfter cooling
  3. concentrationthe solution was concentrated in vacuo to ca. 20 ml
  4. additiondiluted with water (40 ml)
  5. washThe mixture was then washed with ethyl acetate (2×40 ml)
  6. extractionThe solution was then extracted with ethyl acetate (3×50 ml)
  7. concentrationdried organic extracts, were concentrated onto FCC silica
  8. custompurified by FCC
  9. washeluting with System A (150:8:1)
  10. customto give a solid
  11. customtriturated with ether

Sources & evidence

ORD record
ord-dfc3d34e4112456e9b25b876bb9e74b9
Source dataset
uspto-grants-1994_11
Patent number
US05360800

Reaction notes

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