Cesium carbonate → Methyl 4-[(4-ethylphenyl)amino]-5-methylthiothiophene-2-carboxylate

HRID 2298685Notes

Reaction equation

HRID 2298685 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:8]([O:10][CH3:11])=[S:9])[S:5][C:6]=1[CH3:7].C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+].[CH2:64]([C:66]1[CH:72]=[CH:71][C:69]([NH2:70])=[CH:68][CH:67]=1)[CH3:65]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:64]([C:66]1[CH:72]=[CH:71][C:69]([NH:70][C:2]2[CH:3]=[C:4]([C:8]([O:10][CH3:11])=[S:9])[S:5][C:6]=2[CH3:7])=[CH:68][CH:67]=1)[CH3:65]

Participants

6

Reactant 4

HCID 10796Cesium carbonateHCID 115044-EthylanilineHCID 634876Binap, (A+-)-HCID 86583861Methyl 4-bromo-5-methylthiothiophene-2-carboxylate

Product 1

HCID 86583863Methyl 4-[(4-ethylphenyl)amino]-5-methylthiothiophene-2-carboxylateYield 12.8%

Reagents, catalysts & solvents 1

HCID 167845palladium(II) acetateCatalyst

Conditions

Temperature
100 °C

Procedure

To an oven-dried glass vial with stir bar was added a mixture of 100 mg (0.374 mmol) of methyl 4-bromo-5-methylthiothiophene-2-carboxylate (as prepared in Example 241, step (a)), 5.8 mg (6.9 mol %) of palladium (II) acetate, 21.7 mg (9.3 mol %) of racemic-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl, 171.5 mg (0.526 mmol) of cesium carbonate and 59 mg (0.487 mmol) of 4-ethylaniline. The vial was transferred to a glove bag, flushed with dry argon and anhydrous toluene (749 μL) was added. The vial was capped with a Teflon-lined screw cap and heated at 100° C. for 48 h. The cooled suspension was filtered (Celite) washing with ethyl acetate (2×2 mL), and the solvents removed in vacuo. The resulting residue was purified on 1 mm silica prep plates eluting with 40% methylene chloride-hexanes to afford 14 mg (12%) of methyl 4-[(4-ethylphenyl)amino]-5-methylthiothiophene-2-carboxylate as a pale yellow resin which was used directly in the following step.

Workup

  1. additionwas added
  2. customThe vial was transferred to a glove
  3. custombag, flushed with dry argon and anhydrous toluene (749 μL)
  4. additionwas added
  5. customThe vial was capped with a Teflon-
  6. customcap
  7. filtrationThe cooled suspension was filtered (Celite)
  8. washwashing with ethyl acetate (2×2 mL)
  9. customthe solvents removed in vacuo
  10. customThe resulting residue was purified on 1 mm silica
  11. washeluting with 40% methylene chloride-hexanes

Sources & evidence

ORD record
ord-8f2aee92eaa64d36a9ea5501ff5cd99f
Source dataset
uspto-grants-2002_12
Patent number
US06492403B1

Reaction notes

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