P-Anisidine → HCID 86758694, compound

HRID 2298686Notes

Reaction equation

HRID 2298686 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+].[CH3:64][O:65][C:66]1[CH:71]=[CH:70][C:69]([NH2:72])=[CH:68][CH:67]=1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:64][O:65][C:66]1[CH:71]=[CH:70][C:69]([NH:72][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

Participants

6

Reactant 4

HCID 7732P-AnisidineHCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 86583861Methyl 4-bromo-5-methylthiothiophene-2-carboxylate

Product 1

HCID 86758694HCID 86758694, compoundYield 63%

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 120 mg (0.449 mmol) of methyl 4-bromo-5-methylthiothiophene-2-carboxylate (as prepared in Example 241, step (a)), 7.1 mg (7 mol %) of palladium (II) acetate, 29.4 mg (10.5 mol %) of racemic-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl, 205 mg (0.629 mmol) of cesium carbonate and 69.1 mg (0.561 mmol) of p-anisidine. The vial was transferred to a glove bag, flushed with dry argon and anhydrous toluene (0.9 mL) was added. The vial was capped with a Teflon-lined screw cap and heated at 100° C. for 48 h. To the cooled suspension was added ethyl acetate (4 mL), the mixture filtered (Celite) washing with ethyl acetate (2×2 mL), and the solvents removed in vacuo. The resulting residue was purified by silica gel preparative thin layer chromatography (40% CH2Cl2 in hexane) to afford 83 mg (60%) of the title compound as a yellow oil. 1H-NMR (CDCl3, 400 MHz) δ2.39 (s, 3H), 3.82 (s, 3H), 3.87 (s, 3H), 6.03 (s, 1H), 6.89 (m, 2H), 7.03 (m, 2H), 7.58 (s, 1H).

Workup

  1. additionwas added
  2. customThe vial was transferred to a glove
  3. custombag, flushed with dry argon and anhydrous toluene (0.9 mL)
  4. additionwas added
  5. customThe vial was capped with a Teflon-
  6. customcap
  7. additionTo the cooled suspension was added ethyl acetate (4 mL)
  8. filtrationthe mixture filtered (Celite)
  9. washwashing with ethyl acetate (2×2 mL)
  10. customthe solvents removed in vacuo
  11. customThe resulting residue was purified by silica gel preparative thin layer chromatography (40% CH2Cl2 in hexane)

Sources & evidence

ORD record
ord-f4ff6e496f8e4cf085430f2bf41f82c8
Source dataset
uspto-grants-2002_12
Patent number
US06492403B1

Reaction notes

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