Acetic Acid → Troglitazone

HRID 1940679Notes

Reaction equation

HRID 1940679 reaction equation
[OH:1][C:2]1[C:3]([CH3:31])=[C:4]2[C:9](=[C:10]([CH3:13])[C:11]=1[CH3:12])[O:8][C:7]([CH2:15][O:16][C:17]1[CH:30]=[CH:29][C:20]([CH2:21][CH:22]3[S:26][C:25](=N)[NH:24][C:23]3=[O:28])=[CH:19][CH:18]=1)([CH3:14])[CH2:6][CH2:5]2.C(O)(=[O:34])C.Cl.C(=O)(O)[O-].[Na+]>O>[OH:1][C:2]1[C:3]([CH3:31])=[C:4]2[C:9](=[C:10]([CH3:13])[C:11]=1[CH3:12])[O:8][C:7]([CH2:15][O:16][C:17]1[CH:30]=[CH:29][C:20]([CH2:21][CH:22]3[S:26][C:25](=[O:34])[NH:24][C:23]3=[O:28])=[CH:19][CH:18]=1)([CH3:14])[CH2:6][CH2:5]2

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 313Hydrochloric AcidHCID 516892Sodium BicarbonateHCID 1403415895-[[4-[(6-Hydroxy-2,5,7,8-tetramethyl-3,4-dihydrochromen-2-yl)methoxy]phenyl]methyl]-2-imino-1,3-thiazolidin-4-one

Product 1

HCID 5591Troglitazone

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

15.5 g of 5-[4-(6-hydroxy-2,5,7,8-tetramethyl chroman-2-yl-methoxy) benzyl]-2-iminothiazolidine-4-one, prepared by the process as described in Example-1, was added to a mixture of 225 ml of acetic acid, 75 ml of conc. hydrochloric acid and 40 ml of water and the mixture was refluxed for 12 hrs. The reaction mixture was cooled to room temperature and 66.2 g of sodium bicarbonate was added and once the evolution of carbondioxide had ceased, the solvent was distilled off applying high vacuum. A 10:1 by volume mixture of benzene and ethyl acetate was added to the residue and the crude product was washed with a mixture of equal volumes of a saturated aq. sodium bicarbonate solution & water. The organic layer was dried over anhydrous sodium sulphate and the solvent was distilled off. The resulting crude product was quickly eluted tom a silica gel column with 50% ethylacetate-hexane to furnish 12.5 g of the required 5-{4-(6-hydroxy-2, 5, 7, 8-tetramethylchroman-2-yl-methoxy) benzyl) thiazolidine-2,4-dione (Troglitazone) with a HPLC purity of ~67-70%.

Workup

  1. temperaturethe mixture was refluxed for 12 hrs
  2. distillationthe solvent was distilled off
  3. additionA 10:1 by volume mixture of benzene and ethyl acetate
  4. additionwas added to the residue
  5. washthe crude product was washed with a mixture of equal volumes of a saturated aq. sodium bicarbonate solution & water
  6. dry with materialThe organic layer was dried over anhydrous sodium sulphate
  7. distillationthe solvent was distilled off
  8. washThe resulting crude product was quickly eluted tom a silica gel column with 50% ethylacetate-hexane

Sources & evidence

ORD record
ord-5cbcd69b7e904829b09748615b058ea0
Source dataset
uspto-grants-1997_12
Patent number
US05700820

Reaction notes

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