Methyl iodide → HCID 22718134, compound

HRID 2227728Notes

Reaction equation

HRID 2227728 reaction equation
C([C:3]1[N:4]([CH3:23])[CH:5]=[C:6]([C:8]2[CH:13]=[CH:12][C:11]([O:14][C:15]3[CH:20]=[CH:19][C:18]([F:21])=[CH:17][C:16]=3[F:22])=[CH:10][CH:9]=2)[N:7]=1)#N.FC1C=C(F)C=CC=1OC1C=CC(C2N=CNC=2)=CC=1.[OH-].[K+].CI>>[F:22][C:16]1[CH:17]=[C:18]([F:21])[CH:19]=[CH:20][C:15]=1[O:14][C:11]1[CH:10]=[CH:9][C:8]([C:6]2[N:7]=[CH:3][N:4]([CH3:23])[CH:5]=2)=[CH:13][CH:12]=1

Participants

5

Reactant 4

HCID 6328Methyl iodideHCID 14797Potassium HydroxideHCID 22718090HCID 22718090, compoundHCID 178505883HCID 178505883, compound

Product 1

HCID 22718134HCID 22718134, compound

Procedure

2-Cyano-4-[4-(2,4-difluorophenoxy)phenyl]-1-methyl-1H-imidazole. A mixture of crude 4-[4-(2,4-difluorophenoxy)phenyl]-1H-imidazole (prepared from 4.14 g of 2-bromo-1-[4-(2,4-difluorophenoxy)phenyl]ethanone and 35 mL of formamide as described above), solid KOH (2.57 g) and MeI (1 mL) was heated at reflux overnight. After filtration, the reaction was concentrated to dryness and the residue was purified by flash chromatography, affording 4-[4-(2,4-difluorophenoxy)phenyl]-1-methyl-1H-imidazole as a solid. A solution of 4-(dimethylamino)pyridine (1.34 g, 10.9 mmol) in 30 mL of dry DMF at −10° C. was added cyanogen bromide (5.0 M solution in MeCN; 2.1 mL, 10.5 mmol), giving a pale yellow precipitate. Solid 4-[4-(2,4-difluorophenoxy)phenyl]-1-methyl-1H-imidazole (1.39 g, 4.86 mmol) was added and the reaction was heated at 60° C. overnight. The reaction was allowed to cool to room temperature and added to water and EtOAc. The separated aqueous layer was extracted twice with EtOAc and the pooled organic layers were washed with water (3×), dried (Na2SO4), filtered and concentrated. The oily residue was purified by flash chromatography (gradient from 8.5/2.5 to 7/3 hexane/EtOAc) affording 713 mg of 2-cyano-4-[4-(2,4-difluorophenoxy)phenyl]-1-methyl-1H-imidazole as a solid, mp 109-110° C. (Rf 0.42, 7/3 hexane/EtOAc) along with 122 mg of 4-cyano-4-[4-(2,4-difluorophenoxy)phenyl]-1-methyl-1H-imidazole, mp 169-170° C. (Rf 0.32, 7/3 hexane/EtOAc). 1H NMR (2-cyano; CDCl3): δ7.65 (d, 2H, J=9.0 Hz), 7.16 (s, 1H), 7.06 (dt, 1H, J=9.3, 5.4 Hz), 6.93 (d, 2H, J=8.7 Hz), 6.98-6.80 (m, 2H), 3.65 (s, 3H). 1H NMR (4-cyano; CDCl3): δ7.69 (d, 2H, J=8.7 Hz), 7.27 (s, 1H), 7.09 (dt, J=8.7, 5.7 Hz), 6.96 (d, 2H, J=8.7 Hz), 7.00-6.82 (m, 2H), 3.90 (s, 3H).

Workup

  1. temperaturewas heated
  2. temperatureat reflux overnight
  3. filtrationAfter filtration
  4. concentrationthe reaction was concentrated to dryness
  5. customthe residue was purified by flash chromatography

Sources & evidence

ORD record
ord-9295f852c417438cb1564c2f74a4a82c
Source dataset
uspto-grants-2002_07
Patent number
US06414011B1

Reaction notes

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