Water → HCID 22718090, compound

HRID 1582707Notes

Reaction equation

HRID 1582707 reaction equation
[N:1]#[C:2]Br.[F:4][C:5]1[CH:23]=[C:22]([F:24])[CH:21]=[CH:20][C:6]=1[O:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[N:15]=[CH:16][N:17]([CH3:19])[CH:18]=2)=[CH:10][CH:9]=1.O.CCOC(C)=O>CN(C)C1C=CN=CC=1.CN(C=O)C>[C:2]([C:16]1[N:17]([CH3:19])[CH:18]=[C:14]([C:11]2[CH:10]=[CH:9][C:8]([O:7][C:6]3[CH:20]=[CH:21][C:22]([F:24])=[CH:23][C:5]=3[F:4])=[CH:13][CH:12]=2)[N:15]=1)#[N:1].[C:2]([C:14]1([C:11]2[CH:10]=[CH:9][C:8]([O:7][C:6]3[CH:20]=[CH:21][C:22]([F:24])=[CH:23][C:5]=3[F:4])=[CH:13][CH:12]=2)[CH2:18][N:17]([CH3:19])[CH:16]=[N:15]1)#[N:1]

Participants

8

Reactant 4

HCID 962WaterHCID 8857Ethyl AcetateHCID 10476Cyanogen BromideHCID 22718134HCID 22718134, compound

Product 2

HCID 22718090HCID 22718090, compoundHCID 22718112HCID 22718112, compound

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

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): δ 7.65 (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): δ 7.69 (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. customgiving a pale yellow precipitate
  2. temperatureto cool to room temperature
  3. extractionThe separated aqueous layer was extracted twice with EtOAc
  4. washthe pooled organic layers were washed with water (3×)
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe oily residue was purified by flash chromatography (gradient from 8.5/2.5 to 7/3 hexane/EtOAc)

Sources & evidence

ORD record
ord-efd7319ba2fb4dcc8d58837500c0d94e
Source dataset
uspto-grants-2004_05
Patent number
US06737418B2

Reaction notes

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