Hydrochloric Acid → Leriglitazone

HRID 1756625Notes

Reaction equation

HRID 1756625 reaction equation
Br[CH:2]([CH2:7][C:8]1[CH:13]=[CH:12][C:11]([O:14][CH2:15][CH2:16][C:17]2[CH:22]=[CH:21][C:20]([CH:23]([O:25]COC)[CH3:24])=[CH:19][N:18]=2)=[CH:10][CH:9]=1)[C:3]([O:5]C)=O.[NH2:29][C:30](N)=[S:31].C([O-])(=[O:35])C.[Na+].Cl>C(O)C>[OH:25][CH:23]([C:20]1[CH:21]=[CH:22][C:17]([CH2:16][CH2:15][O:14][C:11]2[CH:10]=[CH:9][C:8]([CH2:7][CH:2]3[S:31][C:30](=[O:35])[NH:29][C:3]3=[O:5])=[CH:13][CH:12]=2)=[N:18][CH:19]=1)[CH3:24]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 517045Sodium AcetateHCID 2723790ThioureaHCID 10647271HCID 10647271, compound

Product 1

HCID 4147757LeriglitazoneYield 66.6%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mixture of methyl 2-bromo-3-[4-[2-[5-(1-methoxymethoxyethyl)-2-pyridyl]ethoxy]phenyl]propionate (27.0 g), thiourea (4.6 g), sodium acetate (4.9 g) and ethanol (250 ml) was heated under reflux for 4 hours. To the reaction mixture was added 2N hydrochloric acid (250 ml). The mixture was further heated under reflux for 20 hours and concentrated under reduced pressure. The residue was neutralized with saturated aqueous sodium bicarbonate solution and extracted with ethyl acetate. The ethyl acetate layer was washed with water, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The oily residue thus obtained was subjected to silica gel column chromatography. A fraction eluted with chloroform-methanol (40:1, v/v) gave 5-[4-[2-[5-(1-hydroxyethyl)-2-pyridyl]ethoxy]benzyl]-2,4-thiazolidinedione (14.8 g, yield: 66%). This crude compound was recrystallized from ethanol to obtain colorless prisms, m.p. 155°-156° C.

Workup

  1. temperaturewas heated
  2. temperatureunder reflux for 4 hours
  3. temperatureThe mixture was further heated
  4. temperatureunder reflux for 20 hours
  5. concentrationconcentrated under reduced pressure
  6. extractionextracted with ethyl acetate
  7. washThe ethyl acetate layer was washed with water
  8. dry with materialdried over anhydrous magnesium sulfate
  9. concentrationconcentrated under reduced pressure
  10. customThe oily residue thus obtained
  11. washA fraction eluted with chloroform-methanol (40:1

Sources & evidence

ORD record
ord-c4ec833e53bb46e788f50daa01a13b18
Source dataset
uspto-grants-1995_08
Patent number
US05441971

Reaction notes

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