Diisopropyl Ether → 1-(2-Fluoro-4-methoxyphenyl)-2,5-dimethyl-1H-pyrrole

HRID 1385509Notes

Reaction equation

HRID 1385509 reaction equation
[F:1][C:2]1[CH:7]=[C:6](I)[CH:5]=[CH:4][C:3]=1[N:9]1[C:13]([CH3:14])=[CH:12][CH:11]=[C:10]1[CH3:15].C[O-].[Na+].[CH:19]([O:22]C(C)C)(C)C.[NH4+].[Cl-]>CO.CN(C=O)C.Cl[Cu].O>[F:1][C:2]1[CH:7]=[C:6]([O:22][CH3:19])[CH:5]=[CH:4][C:3]=1[N:9]1[C:13]([CH3:14])=[CH:12][CH:11]=[C:10]1[CH3:15]

Participants

9

Reactant 4

HCID 7914Diisopropyl EtherHCID 25517Ammonium ChlorideHCID 10942334Sodium MethoxideHCID 153546301-(2-Fluoro-4-iodophenyl)-2,5-dimethyl-1H-pyrrole

Product 1

HCID 153546361-(2-Fluoro-4-methoxyphenyl)-2,5-dimethyl-1H-pyrroleYield 62%

Reagents, catalysts & solvents 4

HCID 62652Cuprous chlorideCatalystHCID 887MethanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

The crude product from the previous reaction (1-(2-fluoro-4-iodo-phenyl)-2,5-dimethyl-1 H-pyrrole, 70.0 g, 222 mmol) was dissolved in 230 mL of MeOH and 70 mL of DMF. To this solution was added NaOMe (35.9 g, 666 mmol, 3.0 eq) and CuCl (3.3 g, 31 mmol, 15 mol %). The resulting mixture was warmed to reflux for 4 h. After cooling to room temperature, isopropyl ether (IPE) (500 mL), 5% aqueous NH4Cl (220 mL), and water (350 mL) were added, and the mixture was stirred overnight. The mixture was then filtered through celite, the layers were separated, and the aqueous layer extracted with 350 mL of IPE. The combined organic extracts were then washed with 10% aqueous NH4OH (200 mL), and passed through a pad of silica gel (100 g). Concentration provided a brown oil, which crystallized upon standing (45.2 g, 93% yield). Recrystallization from 135 mL of hot hexane provided 30.1 g (62% yield) of product as a brown solid, m.p. 67-69° C. 1H NMR (CDCl3): d 7.12 (t, J=8 Hz, 1H), 6.75 (d, J=8 Hz, 1H), 6.73 (s, 1H), 5.89 (s, 2H), 3.82 (s, 3H), 1.97 (s, 6H); 13C NMR (CDCl3) (9 of 10 lines observed) d 159.1 (d, J=260 Hz), 130.7, 129.5, 109.9 (d, J=3 Hz), 106.0, 105.6, 102.3 (d, J=25 Hz), 55.7, 12.4; MS (El): m/z 219 (100).

Workup

  1. temperatureThe resulting mixture was warmed
  2. temperatureto reflux for 4 h
  3. filtrationThe mixture was then filtered through celite
  4. customthe layers were separated
  5. extractionthe aqueous layer extracted with 350 mL of IPE
  6. washThe combined organic extracts were then washed with 10% aqueous NH4OH (200 mL)
  7. concentrationConcentration
  8. customprovided a brown oil, which
  9. customcrystallized
  10. customRecrystallization from 135 mL of hot hexane

Sources & evidence

ORD record
ord-bbfa5a29b5fd4851af53f7f7b11e204a
Source dataset
uspto-grants-2001_07
Patent number
US06262272B1

Reaction notes

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