Dimethyl Sulfoxide → Azemiglitazone

HRID 2274339Notes

Reaction equation

HRID 2274339 reaction equation
[OH:1][CH:2]([C:19]1[CH:24]=[CH:23][CH:22]=[C:21]([O:25][CH3:26])[CH:20]=1)[CH2:3][O:4][C:5]1[CH:18]=[CH:17][C:8]([CH2:9][CH:10]2[S:14][C:13](=[O:15])[NH:12][C:11]2=[O:16])=[CH:7][CH:6]=1.CS(C)=O.O=P12OP3(OP(OP(O3)(O1)=O)(=O)O2)=O.C(N(CC)CC)C>C(Cl)Cl.O>[CH3:26][O:25][C:21]1[CH:20]=[C:19]([C:2](=[O:1])[CH2:3][O:4][C:5]2[CH:18]=[CH:17][C:8]([CH2:9][CH:10]3[S:14][C:13](=[O:15])[NH:12][C:11]3=[O:16])=[CH:7][CH:6]=2)[CH:24]=[CH:23][CH:22]=1

Participants

7

Reactant 4

HCID 679Dimethyl SulfoxideHCID 8471TriethylamineHCID 14812Phosphorus oxide (P4O10)HCID 469110405-{4-[2-Hydroxy-2-(3-methoxyphenyl)ethoxy]benzyl}-1,3-thiazolidine-2,4-dione

Product 1

HCID 25230266AzemiglitazoneYield 54%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a stirring solution of 5-{4-[2-hydroxy-2-(3-methoxyphenyl)ethoxy]benzyl}-1,3-thiazolidine-2,4-dione (0.62 g, 1.7 mmol) in DCM (15 mL) was added DMSO (0.5 mL) and the solution was cooled to 0° C. Added phosphorus pentoxide (0.52 g, 1.8 mmol) followed by triethylamine (1.2 mL, 8.3 mmol). The reaction was allowed to slowly warm to RT. After 2 hours water was added and the phases were separated. The pH of the aqueous phase was adjusted to ca. 7 with 2M NaOH. The aqueous phase was extracted with EtOAc. The combined extracts were washed with brine, dried (Na2SO4), filtered and evaporated in vacuo. The resulting white solid was chromatographed on a small silica gel column eluting with 10% EtOAc/DCM. Fractions containing product were combined and evaporated in vacuo to give 0.33 g (54%) of the title compound as a white solid. MS (ESI+) for C19H17NO5S m/z 372.0 (M+H)+. MS (ESI−) for C19H17NO5S m/z 370.1 (M−H)−.

Workup

  1. temperatureto slowly warm to RT
  2. customthe phases were separated
  3. extractionThe aqueous phase was extracted with EtOAc
  4. washThe combined extracts were washed with brine
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. customevaporated in vacuo
  8. customThe resulting white solid was chromatographed on a small silica gel column
  9. washeluting with 10% EtOAc/DCM
  10. additionFractions containing product
  11. customevaporated in vacuo

Sources & evidence

ORD record
ord-4ed74905255043c6b8ef983d8ec86098
Source dataset
uspto-grants-2015_09
Patent number
US09126959B2

Reaction notes

Loading…