Acetic Acid → Ciglitazone

HRID 475525Notes

Reaction equation

HRID 475525 reaction equation
CC(=NO)C(C)=NO.[BH4-].[Na+].[CH3:11][C:12]1([CH2:18][O:19][C:20]2[CH:33]=[CH:32][C:23]([CH:24]=[C:25]3[S:29][C:28](=[O:30])[NH:27][C:26]3=[O:31])=[CH:22][CH:21]=2)[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]1.C(O)(=O)C>O.[OH-].[Na+].C1COCC1.CN(C=O)C>[CH3:11][C:12]1([CH2:18][O:19][C:20]2[CH:33]=[CH:32][C:23]([CH2:24][CH:25]3[S:29][C:28](=[O:30])[NH:27][C:26]3=[O:31])=[CH:22][CH:21]=2)[CH2:13][CH2:14][CH2:15][CH2:16][CH2:17]1

Participants

8

Reactant 4

HCID 176Acetic AcidHCID 4311764Sodium borohydrideHCID 579718655-(4-((1-Methylcyclohexyl)methoxy)benzylidene)thiazolidine-2,4-dioneHCID 135459645Dimethylglyoxime

Product 1

HCID 2750Ciglitazone

Reagents, catalysts & solvents 3

HCID 14798Sodium HydroxideCatalystHCID 962WaterSolvent2×HCID 21974620tetrahydrofuran N,N-dimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To the suspension containing CoCl2.6H2O (4.5 mg, 0.016 mmol) and dimethylglyoxime (70.1 mg, 0.6 mmol) in 10 ml of water, 4 drops of 1.0N NaOH and NaBH4 (384.6 mg, 10 mmol) were subsequently added. The mixture was cooled to 0° C., and 5-(4-((1-methylcyclohexyl)methoxy)benzylidene)thiazolidine-2,4-dione (1 g, 3.0 mmol) in 15 ml of THF-DMF (2:1) was then added thereto over 20 minutes. The mixture was stirred at room temperature for 18 hours, to which acetic acid was then added until the pH thereof reached about 6. The mixture was diluted with water, and extracted with ethyl acetate and water. The organic layer was washed with water several times, dried with anhydrous magnesium sulfate, filtered and solvent-evaporated. The residual oil was chromatographed on silica gel to afford 5-(4-((1-methylcyclohexyl)methoxy)benzyl)thiazolidine-2,4-dione (Derivative 112 of the above formula) as white solid (0.8 g, yield: 80%).

Workup

  1. additionwere subsequently added
  2. additionwas then added until the pH
  3. extractionextracted with ethyl acetate and water
  4. washThe organic layer was washed with water several times
  5. dry with materialdried with anhydrous magnesium sulfate
  6. filtrationfiltered
  7. customsolvent-evaporated
  8. customThe residual oil was chromatographed on silica gel

Sources & evidence

ORD record
ord-37980f75a3e84fb8a0685a620fad8b39
Source dataset
uspto-grants-2014_01
Patent number
US08637558B2

Reaction notes

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