Dimethylformamide → 5,6-Dichloro-1-pyridin-2-ylmethyl-2-(2-trifluoromethyl-[1,3]dioxin-2-yl)-1H-benzimidazole

HRID 2273299Notes

Reaction equation

HRID 2273299 reaction equation
[Cl:1][C:2]1[C:19]([Cl:20])=[CH:18][C:5]2[NH:6][C:7]([C:9]3([C:14]([F:17])([F:16])[F:15])[O:13][CH2:12][CH2:11][O:10]3)=[N:8][C:4]=2[CH:3]=1.[H-].[Na+].Br.Br[CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][N:27]=1.[CH3:32]N(C=O)C>C(OCC)(=O)C.C(OCC)C>[Cl:1][C:2]1[C:19]([Cl:20])=[CH:18][C:5]2[N:6]([CH2:25][C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][N:27]=3)[C:7]([C:9]3([C:14]([F:16])([F:15])[F:17])[O:10][CH2:11][CH:32]=[CH:12][O:13]3)=[N:8][C:4]=2[CH:3]=1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 27347202-(Bromomethyl)pyridine hydrobromideHCID 166648615,6-Dichloro-2-(2-trifluoromethyl-[1,3]dioxolan-2-yl)-1H-benzimidazole

Product 1

HCID 671034665,6-Dichloro-1-pyridin-2-ylmethyl-2-(2-trifluoromethyl-[1,3]dioxin-2-yl)-1H-benzimidazole

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8857Ethyl AcetateSolvent

Procedure

5,6-Dichloro-2-(2-trifluoromethyl-[1,3]dioxolan-2-yl)-1H-benzimidazole (0.37 g; 1.1 mmol) was dissolved in DMF (6 mL), treated with 60% NaH in mineral oil 9.14 g; 3.5 mmol) and stirred under a nitrogen atmosphere for 20 minutes. Subsequently, 2-(Bromomethyl)pyridine hydrobromide (0.44 g; 1.7 mmol) was added to the reaction mixture and stirred at room temperature overnight. The reaction mixture was diluted with ethyl acetate (25 mL) and diethyl ether (25 mL), washed with water (30 mL) and brine (3×30 mL), then dried over Na2SO4. The concentrated crude material was purified by column chromatography (SiO2; 50% ethyl acetate/hexanes) to yield the title compound as an off-white solid.

Workup

  1. stirringstirred at room temperature overnight
  2. washwashed with water (30 mL) and brine (3×30 mL)
  3. dry with materialdried over Na2SO4
  4. concentrationThe concentrated crude material
  5. customwas purified by column chromatography (SiO2; 50% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-86b2afb02da3469ba597b40ba72c8276
Source dataset
uspto-grants-2015_09
Patent number
US09120830B2

Reaction notes

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