Hydrochloric Acid → Troglitazone

HRID 1940678Notes

Reaction equation

HRID 1940678 reaction equation
C([O:3][C:4](=O)[CH:5](Cl)[CH2:6][C:7]1[CH:12]=[CH:11][C:10]([O:13][CH2:14][C:15]2([CH3:32])[CH2:24][CH2:23][C:22]3[C:17](=[C:18]([CH3:31])[C:19]([CH3:30])=[C:20]([O:26]C(=O)C)[C:21]=3[CH3:25])[O:16]2)=[CH:9][CH:8]=1)C.[NH2:35][C:36](N)=[S:37].S1(CCCC1)(=O)=[O:40].Cl.C(=O)(O)[O-].[Na+]>O.C(O)(=O)C>[OH:26][C:20]1[C:21]([CH3:25])=[C:22]2[C:17](=[C:18]([CH3:31])[C:19]=1[CH3:30])[O:16][C:15]([CH2:14][O:13][C:10]1[CH:9]=[CH:8][C:7]([CH2:6][CH:5]3[S:37][C:36](=[O:40])[NH:35][C:4]3=[O:3])=[CH:12][CH:11]=1)([CH3:32])[CH2:24][CH2:23]2

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 31347SulfolaneHCID 516892Sodium BicarbonateHCID 2723790ThioureaHCID 13605832HCID 13605832, compound

Product 1

HCID 5591Troglitazone

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 962WaterSolvent

Procedure

A mixture of 70 g of ethyl-3-[4-(6-acetoxy-2,5,7,8-tetramethylchroman-2-ylmethoxy)phenyl]-2-chloropropionate, 13.12 g of thiourea and 80.2 ml of sulpholane was reacted for 80 min., under a nitrogen stream at 115°-120° C. Subsequently, a 656.2 ml Acetic acid, 218.7 ml conc. hydrochloric acid and 109.4 ml water was added to this and the resulting mixture was further heated for 12 hrs at 85°-90° C. The reaction mixture was cooled to room temperature and 196.8 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 from a silica gel column with 50% ethylacetate-hexane to furnish 40 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%. The elution of column was continued further to yield 5-[4-(6-hydroxy-2,5,7,8-tetramethylchroman-2-yl-methoxy)benzyl]2-iminothiazolidine-4-one with HPLC purity of ~70%.

Workup

  1. customwas reacted for 80 min., under a nitrogen stream at 115°-120° C
  2. temperaturewas further heated for 12 hrs at 85°-90° C
  3. distillationthe solvent was distilled off
  4. additionA 10:1 by volume mixture of benzene and ethyl acetate
  5. additionwas added to the residue
  6. washthe crude product was washed with a mixture of equal volumes of a saturated aq. sodium bicarbonate solution & water
  7. dry with materialThe organic layer was dried over anhydrous sodium sulphate
  8. distillationthe solvent was distilled off
  9. washThe resulting crude product was quickly eluted from a silica gel column with 50% ethylacetate-hexane

Sources & evidence

ORD record
ord-28c700e274d14a3cbed0ba47ea921f4a
Source dataset
uspto-grants-1997_12
Patent number
US05700820

Reaction notes

Loading…