Sodium Hydroxide → Azemiglitazone

HRID 1427542Notes

Reaction equation

HRID 1427542 reaction equation
O/N=[C:3](/[C:20]1[CH:25]=[CH:24][CH:23]=[C:22]([O:26][CH3:27])[CH:21]=1)\[CH2:4][O:5][C:6]1[CH:19]=[CH:18][C:9]([CH2:10][CH:11]2[S:15][C:14](=[O:16])[NH:13][C:12]2=[O:17])=[CH:8][CH:7]=1.[OH-:28].[Na+].CO.C(Cl)Cl>C1COCC1.Cl>[CH3:27][O:26][C:22]1[CH:21]=[C:20]([C:3](=[O:28])[CH2:4][O:5][C:6]2[CH:19]=[CH:18][C:9]([CH2:10][CH:11]3[S:15][C:14](=[O:16])[NH:13][C:12]3=[O:17])=[CH:8][CH:7]=2)[CH:25]=[CH:24][CH:23]=1

Participants

6

Reactant 3

HCID 14798Sodium HydroxideHCID 21226129Dichloromethane methanolHCID 665542955-[[4-[(2Z)-2-hydroxyimino-2-(3-methoxyphenyl)ethoxy]phenyl]methyl]-1,3-thiazolidine-2,4-dione

Product 1

HCID 25230266Azemiglitazone

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 8028TetrahydrofuranSolvent

Procedure

A stirring solution of 5-(4-{[(2Z)-2-(hydroxyimino)-2-(3-methoxyphenyl)ethyl]oxy}benzyl)-1,3-thiazolidine-2,4-dione (0.76 g, 2.0 mmol; Supplier=Kalexsyn; Lot=1003-TTP-124) in THF (5 ml) and 6M HCl (5 ml) was heated to reflux. Little reaction after 4 hours at reflux. Left to reflux overnight. Reaction is complete. 2N NaOH was added until the reaction mixture was ca. pH 8-9. The reaction mixture was extracted with EtOAc (2×25 ml). The combined extracts were washed with brine, dried (Na2SO4), filtered and evaporated in vacuo to give a light yellow oily solid. This material was treated with 5% MeOH/DCM (10 ml) and the resulting white solids were collected by suction filtration and dried to afford 495 mg of final product. 1H-NMR (DMSO-d6): δ 12.03(s, 1H), 7.62(d, J=7.7 Hz, 1H), 7.49((m, 2H), 7.27(dd, J=8.2, 2.6 Hz, 1H), 7.15(d, J=8.7 Hz, 2H), 6.91(d, J=8.5 Hz, 2H), 5.55(s, 2H), 4.88(dd, J=9.1, 4.3 Hz, 1H), 3.83(s, 3H), 3.31(m, 1H), 3.31(m, 1H), 3.05(dd, J=14.1, 9.3 Hz, 1H). HPLC: 3.782 min., 93 area % @ 210 nm; 3.785 min. 100 area % @ 254 nm. MS (ESI−) for C19H17NO5S m/z 370.1 (M−H)−.

Workup

  1. customLittle reaction after 4 hours
  2. temperatureat reflux
  3. waitLeft
  4. temperatureto reflux overnight
  5. customReaction
  6. extractionThe reaction mixture was extracted with EtOAc (2×25 ml)
  7. washThe combined extracts were washed with brine
  8. dry with materialdried (Na2SO4)
  9. filtrationfiltered
  10. customevaporated in vacuo
  11. customto give a light yellow oily solid
  12. filtrationthe resulting white solids were collected by suction filtration
  13. customdried

Sources & evidence

ORD record
ord-b4ce98a53c29493798a8ecd5d09a7899
Source dataset
uspto-grants-2015_01
Patent number
US08933240B2

Reaction notes

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