Methanol → HCID 9798669, compound

HRID 2084990Notes

Reaction equation

HRID 2084990 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:11](=[O:23])[NH:12][C:13](=[O:22])[C:14]=2[C:15]2[CH:20]=[CH:19][C:18](I)=[CH:17][CH:16]=2)[CH:5]=[CH:6][C:7]=1[CH3:8].CO.[C]=O.C(N(CC)CC)C.[C:35]([O:38][CH2:39]C)(=[O:37])C>[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[F:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:11](=[O:23])[NH:12][C:13](=[O:22])[C:14]=2[C:15]2[CH:20]=[CH:19][C:18]([C:35]([O:38][CH3:39])=[O:37])=[CH:17][CH:16]=2)[CH:5]=[CH:6][C:7]=1[CH3:8]

Participants

7

Reactant 5

HCID 887MethanolHCID 8471TriethylamineHCID 8857Ethyl AcetateHCID 22728604HCID 22728604, compoundHCID 178418416HCID 178418416, compound2×

Product 1

HCID 9798669HCID 9798669, compound

Reagents, catalysts & solvents 1

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalyst

Procedure

A mixture of 3-(3-Fluoro-4-methylphenyl-amino)-4-(4-iodophenyl)-1H-pyrrole-2,5-dione (Example A705, 126 mg, 0.3 mmol), tetrakis(triphenyl phosphine)-palladium(0) (35 mg, 0.03 mmol) and methanol (10 mL) was placed in a 50 mL two necked round bottomed flask. One arm of the flask was sealed with a septum and to the other arm was fitted a reflux condenser, topped with a multiway tap connected respectively to vacuum, a carbon monoxide cylinder and to a balloon. Using the multiway tap, the flask was alternately evacuated and flushed with carbon monoxide, and the process repeated several times to unsure an atmosphere of carbon monoxide within the flask. The balloon was charged with carbon monoxide and this was then opened to the reaction flask for the duration of the reaction in order to maintain a slight positive pressure of carbon monoxide within the flask. Triethylamine (100 uL, 0.7 mmol) was added and the mixture heated at reflux for 16 hours. The mixture was cooled and diluted with ethyl acetate and the resulting solution washed with aqueous hydrochloric acid (1M, 50 mL), water (50 mL) and brine (50 mL). The organic solution was dried over magnesium sulphate and evaporated to afford a solid. This was chromatographed on silica gel using dichloromethane-ether (98:2 v/v) as eluent to afford the tide compound, a solid.

Workup

  1. customOne arm of the flask was sealed with a septum and to the other arm
  2. customwas fitted a reflux condenser
  3. customthe flask was alternately evacuated
  4. customflushed with carbon monoxide
  5. additionThe balloon was charged with carbon monoxide
  6. customthis was then opened to the reaction flask for the duration of the reaction in order
  7. temperaturethe mixture heated
  8. temperatureat reflux for 16 hours
  9. temperatureThe mixture was cooled
  10. washthe resulting solution washed with aqueous hydrochloric acid (1M, 50 mL), water (50 mL) and brine (50 mL)
  11. dry with materialThe organic solution was dried over magnesium sulphate
  12. customevaporated
  13. customto afford a solid
  14. customThis was chromatographed on silica gel
  15. customto afford the tide compound

Sources & evidence

ORD record
ord-7ad333588aca4013847ce10a1241b331
Source dataset
uspto-grants-2004_04
Patent number
US06719520B2

Reaction notes

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