Pyrrole → 1-(2-Fluoro-4-iodophenyl)-2,5-dimethyl-1H-pyrrole

HRID 1385508Notes

Reaction equation

HRID 1385508 reaction equation
[F:1][C:2]1[CH:8]=[C:7]([I:9])[CH:6]=[CH:5][C:3]=1[NH2:4].C[C:11]1[CH:12]=[CH:13][C:14](S(O)(=O)=O)=[CH:15][CH:16]=1.O.C(CC(=O)C)C(C)=O.N1C=CC=C1>C1(C)C=CC=CC=1>[F:1][C:2]1[CH:8]=[C:7]([I:9])[CH:6]=[CH:5][C:3]=1[N:4]1[C:15]([CH3:14])=[CH:16][CH:11]=[C:12]1[CH3:13]

Participants

6

Reactant 4

HCID 8027PyrroleHCID 80352,5-HexanedioneHCID 1856942-Fluoro-4-iodoanilineHCID 521998p-Toluenesulfonic acid monohydrate

Product 1

HCID 153546301-(2-Fluoro-4-iodophenyl)-2,5-dimethyl-1H-pyrrole

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A 500 mL round bottom flask was charged with 2-fluoro-4-iodoaniline (53.3 g, 220 mmol), toluene (250 mL), TsOH·H2O (0.43 g, 2.3 mmol, 1 mol %), and acetonylacetone (30.8 g, 270 mmol, 1.2 eq). The solution was warmed to reflux under Dean-Stark conditions for 1 h, at which point GC/MS and TLC analysis indicate complete conversion to the pyrrole. The solution is cooled to room temperature, washed with aqueous NaHCO3, dried over MgSO4, filtered, and concentrated to provide a dark brown oil which crystallized upon standing (crude yield=72.8 g, 103% of theory). This material was homogeneous by HPLC and 1H nmr, and was suitable for use in the next reaction. An analytical sample was prepared by dissolving in 210 mL of hot hexanes, cooling, then concentrating to 50% of the original volume. Cooling in an ice bath with rapid stirring provided 35.5 g (49% recovery) of a brown, granular solid (m.p. 68-70° C.). 1H NMR (CDCl3): d 7.43 (t, J=27 Hz, 2H), 7.13 (t, J=20 Hz, 1H), 5.94 (s, 2H), 2.02 (s, 6H); 13C NMR (CDCl3) d 158.3 (d, J=254 Hz), 131.6, 128.9, 127.8 (d, J=3 Hz), 122.0, 120.3 (d, J=23 Hz), 106.4, 12.4; MS (El): m/z 268 (100).

Workup

  1. temperatureThe solution was warmed
  2. temperatureto reflux under Dean-Stark conditions for 1 h, at which point GC/MS and TLC analysis
  3. washwashed with aqueous NaHCO3
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto provide a dark brown oil which
  8. customcrystallized
  9. customwas suitable for use in the next reaction
  10. customAn analytical sample was prepared
  11. temperaturecooling
  12. concentrationconcentrating to 50% of the original volume
  13. temperatureCooling in an ice bath

Sources & evidence

ORD record
ord-c797414c85314dc7a4f51e54e3738a82
Source dataset
uspto-grants-2001_07
Patent number
US06262272B1

Reaction notes

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