2-Methylbenzimidazole → 2-Methylbenzimidazole

HRID 1988149Notes

Reaction equation

HRID 1988149 reaction equation
[CH3:1][C:2]1[NH:3][C:4]2[CH:10]=[CH:9][CH:8]=[CH:7][C:5]=2[N:6]=1.C([Li])CCC.[F:16][C:17]([F:34])([F:33])[C:18](=[O:32])[CH2:19][C:20]([C:23]1[CH:28]=[C:27]([F:29])[CH:26]=[CH:25][C:24]=1[O:30][CH3:31])([CH3:22])[CH3:21].[NH4+].[Cl-]>C1COCC1>[CH3:1][C:2]1[NH:3][C:4]2[CH:10]=[CH:9][CH:8]=[CH:7][C:5]=2[N:6]=1.[NH:3]1[C:4]2[CH:10]=[CH:9][CH:8]=[CH:7][C:5]=2[N:6]=[C:2]1[CH2:1][C:18]([OH:32])([CH2:19][C:20]([C:23]1[CH:28]=[C:27]([F:29])[CH:26]=[CH:25][C:24]=1[O:30][CH3:31])([CH3:22])[CH3:21])[C:17]([F:16])([F:34])[F:33]

Participants

7

Reactant 4

HCID 119842-MethylbenzimidazoleHCID 25517Ammonium ChlorideHCID 100849201,1,1-Trifluoro-4-(5-fluoro-2-methoxyphenyl)-4-methylpentan-2-oneHCID 178418339Butyllithium

Product 2

HCID 119842-MethylbenzimidazoleHCID 10126889HCID 10126889, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 2-methylbenzimidazole (300 mg, 2.3 mmol) in 20 mL of anhydrous THF at −30° C., n-butyl lithium (1.6 M in pentanes, 3 mL, 4.8 mmol) was slowly added. The resulting red-colored heterogeneous mixture was stirred for 2 hours at this temperature, then a solution of 1,1,1-trifluoro-4-(5-fluoro-2-methoxyphenyl)-4-methylpentan-2-one (700 mg, 2.55 mmol) (see Example 1) in anhydrous THF (1 mL) was added dropwise. The reaction temperature was allowed to slowly warm to room temperature over a period of 2 hours, at which time reaction was treated with saturated NH4Cl solution. The resulting mixture was extracted with diethyl ether. The combined organic extracts were dried over magnesium sulfate, filtered, and concentrated in vacuo to afford an oil which was purified by chromatography on silica gel to provide 200 mg of unchanged 2-methylbenzimidazole and 60 mg of the title compound as a white solid, m.p. 80° C.-82° C.

Workup

  1. extractionThe resulting mixture was extracted with diethyl ether
  2. dry with materialThe combined organic extracts were dried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customto afford an oil which
  6. customwas purified by chromatography on silica gel

Sources & evidence

ORD record
ord-085c3b4ff46d43478ced85d9224d1ee0
Source dataset
uspto-grants-2009_06
Patent number
US07553966B2

Reaction notes

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