3-Thiophenecarboxylic acid, tetrahydro-4-oxo-, methyl ester → Methyl 4-[(2-fluoro-4-iodophenyl)amino]-2,5-dihydrothiophene-3-carboxylate

HRID 1809010Notes

Reaction equation

HRID 1809010 reaction equation
O=[C:2]1[CH2:6][S:5][CH2:4][CH:3]1[C:7]([O:9][CH3:10])=[O:8].[F:11][C:12]1[CH:18]=[C:17]([I:19])[CH:16]=[CH:15][C:13]=1[NH2:14]>C(O)C.C(O)(=O)C>[F:11][C:12]1[CH:18]=[C:17]([I:19])[CH:16]=[CH:15][C:13]=1[NH:14][C:2]1[CH2:6][S:5][CH2:4][C:3]=1[C:7]([O:9][CH3:10])=[O:8]

Participants

5

Reactant 2

HCID 984243-Thiophenecarboxylic acid, tetrahydro-4-oxo-, methyl esterHCID 1856942-Fluoro-4-iodoaniline

Product 1

HCID 67051651Methyl 4-[(2-fluoro-4-iodophenyl)amino]-2,5-dihydrothiophene-3-carboxylateYield 42%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidCatalystHCID 702EthanolSolvent

Procedure

To a mixture of methyl 4-oxotetrahydrothiophene-3-carboxylate (1.75 g, 11 mmol) (commercially available or prepared using procedures similar to those described in Rossy et. al. J. Org. Chem. 1980, 45(4), 617-2) in 15 mL of ethanol was added 2-fluoro-4-iodoaniline (2.6 g, 11 mmol) followed by addition of several drops of acetic acid. The mixture was refluxed for 3 hrs. The mixture was cooled to room temperature and the product precipitated. This product was filtered off, washed with ethyl acetate, ether, dried in vacuo to afford the methyl 4-[(2-fluoro-4-iodophenyl)amino]-2,5-dihydrothiophene-3-carboxylate (1.7 g, 42%). 1H NMR (d6-DMSO): 9.80 (s, 1H), 7.71 (d, 1H), 7.49 (dd, 1H), 7.24 (t, 1H), 4.10 (t, 2H), 3.79 (t, 2H), 3.69 (s, 3H); MS (EI) for C12H11FINO2S: 380 (MH+).

Workup

  1. customprepared
  2. temperatureThe mixture was refluxed for 3 hrs
  3. customthe product precipitated
  4. filtrationThis product was filtered off
  5. washwashed with ethyl acetate, ether
  6. customdried in vacuo

Sources & evidence

ORD record
ord-d418a4a9c49146cf99cbb44fcda741f4
Source dataset
uspto-grants-2013_01
Patent number
US08362002B2

Reaction notes

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