Bromoacetonitrile → HCID 22394537, compound

HRID 1071570Notes

Reaction equation

HRID 1071570 reaction equation
[O:1]1[C:5]2[CH:6]=[CH:7][C:8]([C:10]3[N:11]=[C:12]([C:21]4[CH:26]=[CH:25][C:24]([OH:27])=[CH:23][CH:22]=4)[NH:13][C:14]=3[C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][N:16]=3)=[CH:9][C:4]=2[O:3][CH2:2]1.[H-].[Na+].Br[CH2:31][C:32]#[N:33].[Cl-].[NH4+]>O1CCCC1>[O:1]1[C:5]2[CH:6]=[CH:7][C:8]([C:10]3[N:11]=[C:12]([C:21]4[CH:22]=[CH:23][C:24]([O:27][CH2:31][C:32]#[N:33])=[CH:25][CH:26]=4)[NH:13][C:14]=3[C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][N:16]=3)=[CH:9][C:4]=2[O:3][CH2:2]1

Participants

6

Reactant 4

HCID 11534BromoacetonitrileHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 135418450HCID 135418450, compound

Product 1

HCID 22394537HCID 22394537, compoundYield 30.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

4-(4-Benzo[1,3]dioxol-5-yl-5-pyridin-2-yl-1H-imidazol-2-yl)-phenol (357 mg; 1 mmol) was dissolved in tetrahydrofuran (20 ml) under argon and treated portionwise with sodium hydride (60% dispersion in oil; 60 mg; 1.5 mmol). When effervescence had ceased, bromoacetonitrile (178.5 mg; 103.5 μl ; 1.5 mmol) was added and the mixture was stirred at ambient temperature for 18 h. Saturated aqueous ammonium chloride solution was added and the nitrile extracted into ethyl acetate. The organic extracts were combined, washed with water, saturated brine, dried (MgSO4) and evaporated to dryness under reduced pressure. The residue was purified by chromatography through SiO2, eluting with ethyl acetate in 60-80° petroleum ether (50→100% ethyl acetate gradient), to give [4-(4-benzo[1,3]dioxol-5-yl-5-pyridin-2-yl-1H-imidazol-2-yl)-phenoxy]-acetonitrile (120 mg; 30%). This nitrile (120 mg; 0.31 mmol) was treated with ethanol (30 ml) and 2M aq. sodium hydroxide solution and the resulting mixture heated at reflux for 3 h. Cooled and evaporated to dryness under reduced pressure. The residue was treated with water and acidified to pH4-5 with 5M hydrochloric acid. The yellow precipitate was collected by filtration, washed with water and dried at 40° C. under reduced pressure (92 mg; 73%). 1H NMR (250 MHz; CD3OD) δ: 4.77 (2H, s), 6.12 (2H, s), 7.02 (1H, d), 7.12-7.14 (2H, m), 7.18 (2H, d), 7.44-7.49 (1H, m), 7.60 (1H, d), 7.86-7.92 (1H, m), 8.05 (2H, d), 8.72 (1H, d); m/z (API): 416.3 [M+H]⊕.

Workup

  1. extractionthe nitrile extracted into ethyl acetate
  2. washwashed with water, saturated brine
  3. dry with materialdried (MgSO4)
  4. customevaporated to dryness under reduced pressure
  5. customThe residue was purified by chromatography through SiO2
  6. washeluting with ethyl acetate in 60-80° petroleum ether (50→100% ethyl acetate gradient)

Sources & evidence

ORD record
ord-74ed02f1120f4e8a9b6253f9c5661c5c
Source dataset
uspto-grants-2005_06
Patent number
US06906089B2

Reaction notes

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