alpha-Bromo-o-chlorotoluene → 2-[4-Chloro-2-(2-chloro-benzyloxy)-phenyl]-1-cyclohexylmethyl-5,6-difluoro-1H-benzoimidazole

HRID 1875743Notes

Reaction equation

HRID 1875743 reaction equation
[H-].[Na+].[Cl:3][C:4]1[CH:5]=[CH:6][C:7]([C:11]2[N:15]([CH2:16][CH:17]3[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]3)[C:14]3[CH:23]=[C:24]([F:28])[C:25]([F:27])=[CH:26][C:13]=3[N:12]=2)=[C:8]([OH:10])[CH:9]=1.Br[CH2:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=1[Cl:37]>CN(C)C=O>[Cl:3][C:4]1[CH:5]=[CH:6][C:7]([C:11]2[N:15]([CH2:16][CH:17]3[CH2:18][CH2:19][CH2:20][CH2:21][CH2:22]3)[C:14]3[CH:23]=[C:24]([F:28])[C:25]([F:27])=[CH:26][C:13]=3[N:12]=2)=[C:8]([O:10][CH2:30][C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=2[Cl:37])[CH:9]=1

Participants

5

Reactant 3

HCID 11905alpha-Bromo-o-chlorotolueneHCID 24758Sodium hydrideHCID 1363784785-chloro-2-(1-cyclohexylmethyl-5,6-difluoro-1H-benzoimidazol-2-yl)-phenol

Product 1

HCID 582092722-[4-Chloro-2-(2-chloro-benzyloxy)-phenyl]-1-cyclohexylmethyl-5,6-difluoro-1H-benzoimidazoleYield 38%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Procedure

To a suspension of sodium hydride (16 mg, 0.4 mmol, 60%) in dry N,N-dimethylformamide (10 ml) at 25° C. was slowly added a solution of 5-chloro-2-(1-cyclohexylmethyl-5,6-difluoro-1H-benzoimidazol-2-yl)-phenol (0.10 g, 0.275 mmol) in dry N,N-dimethylformamide (5 ml), and was allowed to stir for 0.5 h. A solution of 1-bromomethyl-2-chloro-benzene (82 mg, 0.4 mmol; CAS Reg. No. 611-17-6) in N,N-dimethylformamide (5 ml) was then added drop wise to the above solution, and further stirred for 16 h at 25° C. The reaction mixture was quenched with saturated aqueous solution of ammonium chloride. The solvents were removed under reduced pressure. The crude material dissolved in ethyl acetate, washed with water, and then with brine, dried over sodium sulfate, filtered, and evaporated under reduced pressure. The crude product was purified by column chromatography over silica gel (10-20% ethyl acetate/n-hexane) to afford the title compound as a colorless powder (38%). MS (Turbo Spray): m/z=501.2 (M+H).

Workup

  1. stirringfurther stirred for 16 h at 25° C
  2. customThe reaction mixture was quenched with saturated aqueous solution of ammonium chloride
  3. customThe solvents were removed under reduced pressure
  4. dissolutionThe crude material dissolved in ethyl acetate
  5. washwashed with water
  6. dry with materialwith brine, dried over sodium sulfate
  7. filtrationfiltered
  8. customevaporated under reduced pressure
  9. customThe crude product was purified by column chromatography over silica gel (10-20% ethyl acetate/n-hexane)

Sources & evidence

ORD record
ord-5f929fb510ca48c69f15b11a3832e65b
Source dataset
uspto-grants-2012_11
Patent number
US08309581B2

Reaction notes

Loading…