Diclofenac → S-Diclofenac

HRID 44160

Reaction equation

HRID 44160 reaction equation
[CH:1]1[CH:2]=[CH:3][C:4]([NH:11][C:12]2[C:13]([Cl:19])=[CH:14][CH:15]=[CH:16][C:17]=2[Cl:18])=[C:5]([CH2:7][C:8]([OH:10])=[O:9])[CH:6]=1.OC1C2N=NNC=2C=CC=1.C1CCC(N=C=NC2CCCCC2)CC1.O[C:46]1[CH:51]=[CH:50][C:49]([C:52]2[S:56][S:55][C:54](=[S:57])[CH:53]=2)=[CH:48][CH:47]=1>CN(C)C=O.C(OCC)(=O)C>[S:57]=[C:54]1[S:55][S:56][C:52]([C:49]2[CH:48]=[CH:47][C:46]([O:9][C:8](=[O:10])[CH2:7][C:5]3[CH:6]=[CH:1][CH:2]=[CH:3][C:4]=3[NH:11][C:12]3[C:13]([Cl:19])=[CH:14][CH:15]=[CH:16][C:17]=3[Cl:18])=[CH:51][CH:50]=2)=[CH:53]1

Participants

7

Reactant 4

HCID 3033DiclofenacHCID 10868DicyclohexylcarbodiimideHCID 3082127Desmethylanethol trithioneHCID 178418300HCID 178418300, compound

Product 1

HCID 11948307S-DiclofenacYield 74%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To the solution of 1 (diclofenac, 890 mg, 3.0 mmol) in 50 mL of N,N-dimethylformamide, hydroxybenzotriazole (445 mg, 3.3 mmol) and DCC (680 mg, 3.3 mmol) were added with stirring at 0° C. for 1 h. To the reaction mixture 5-p-hydroxyphenyl-1,2-dithiole-3-thione (2; 678 mg, 3 mmol) was added and stirred for 1 h at 0° C. and 3 h at room temperature. After filtration, the filtrate was evaporated under reduced pressure and the oily residue thus obtained was dissolved in ethyl acetate; the organic layer was washed with brine, dried on anhydrous MgSO4, filtered and the solvent evaporated. The crude product 3 was loaded on a silica gel open column and eluted with CH2Cl2/MeOH (9/1), from which [2-(2,6-dichloro-phenylamino)-phenyl]-acetic acid 4-(5-thioxo-5H-[1,2]dithiol-3-yl)-phenyl ester (3) was obtained (1.1 g, 74% yield).

Workup

  1. stirringstirred for 1 h at 0° C. and 3 h at room temperature
  2. filtrationAfter filtration
  3. customthe filtrate was evaporated under reduced pressure
  4. customthe oily residue thus obtained
  5. washthe organic layer was washed with brine
  6. dry with materialdried on anhydrous MgSO4
  7. filtrationfiltered
  8. customthe solvent evaporated
  9. washeluted with CH2Cl2/MeOH (9/1), from which [2-(2,6-dichloro-phenylamino)-phenyl]-acetic acid 4-(5-thioxo-5H-[1,2]dithiol-3-yl)-phenyl ester (3)
  10. customwas obtained (1.1 g, 74% yield)

Sources & evidence

ORD record
ord-524b1f6b99df4db48a59db8265a7f4eb
Source dataset
uspto-grants-2013_09
Patent number
US08541398B2

Linked notes

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