Acetic Acid → N-Cyclobutyl-5-[2,6-dichloro-4-(2,4-dioxo-thiazolidin-5-ylidenemethyl)-phenoxy]-2-hydroxy-N-methyl-benzamide

HRID 1168098Notes

Reaction equation

HRID 1168098 reaction equation
[CH:1]1([N:5]([CH3:26])[C:6](=[O:25])[C:7]2[CH:12]=[C:11]([O:13][C:14]3[C:19]([Cl:20])=[CH:18][C:17]([CH:21]=O)=[CH:16][C:15]=3[Cl:23])[CH:10]=[CH:9][C:8]=2[OH:24])[CH2:4][CH2:3][CH2:2]1.[CH2:27]1[S:33][C:31](=[O:32])[NH:30][C:28]1=[O:29].C(O)(=O)C.N1CCCCC1>C1(C)C=CC=CC=1>[CH:1]1([N:5]([CH3:26])[C:6](=[O:25])[C:7]2[CH:12]=[C:11]([O:13][C:14]3[C:19]([Cl:20])=[CH:18][C:17]([CH:21]=[C:27]4[S:33][C:31](=[O:32])[NH:30][C:28]4=[O:29])=[CH:16][C:15]=3[Cl:23])[CH:10]=[CH:9][C:8]=2[OH:24])[CH2:2][CH2:3][CH2:4]1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 5437ThiazolidinedioneHCID 8082PiperidineHCID 22285661n-Cyclobutyl-5-(2,6-dichloro-4-formyl-phenoxy)-2-hydroxy-n-methyl-benzamide

Product 1

HCID 86584087N-Cyclobutyl-5-[2,6-dichloro-4-(2,4-dioxo-thiazolidin-5-ylidenemethyl)-phenoxy]-2-hydroxy-N-methyl-benzamideYield 75%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a solution of the title compound of Step H (40 mg, 0.10 mmol) and thiazolidinedione (13 mg, 0.11 mmol) in toluene (2 ml) was added acetic acid (1.5 μl, 0.025 mmol), piperidine (2.5 μl, 0.025 mmol) and powdered 3 A° molecular sieves. The reaction mixture was heated to reflux and stirred at reflux for about 18 hours. The solvent was removed under reduced pressure and the residue was partitioned between ethyl acetate (10 ml) and water (10 ml). The organic layer was washed with 1N HCl (2×10 ml), brine (10 ml), dried, filtered, and concentrated. The crude product was purified by preparative TLC (7% MeOH in dichloromethane) to afford the title compound (37 mg). MS (APCl−) Calc: 492.0, found: 491.0 (M−1).

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux
  3. temperatureat reflux for about 18 hours
  4. customThe solvent was removed under reduced pressure
  5. customthe residue was partitioned between ethyl acetate (10 ml) and water (10 ml)
  6. washThe organic layer was washed with 1N HCl (2×10 ml), brine (10 ml)
  7. customdried
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe crude product was purified by preparative TLC (7% MeOH in dichloromethane)

Sources & evidence

ORD record
ord-9f5cca49733b4845af149fd6149959a9
Source dataset
uspto-grants-2003_09
Patent number
US06620830B2

Reaction notes

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