Sodium hydride → 2-Chloro-1-[[2-(trimethylsilanyl)ethoxy]methyl]-benzimidazole

HRID 538105Notes

Reaction equation

HRID 538105 reaction equation
[H-].[Na+].[Cl:3][C:4]1[NH:5][C:6]2[CH:12]=[CH:11][CH:10]=[CH:9][C:7]=2[N:8]=1.[CH3:13][Si:14]([CH3:21])([CH3:20])[CH2:15][CH2:16][O:17][CH2:18]Cl>C1COCC1>[Cl:3][C:4]1[N:8]([CH2:18][O:17][CH2:16][CH2:15][Si:14]([CH3:21])([CH3:20])[CH3:13])[C:7]2[CH:9]=[CH:10][CH:11]=[CH:12][C:6]=2[N:5]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 785722-ChlorobenzimidazoleHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl ether

Product 1

HCID 597528982-Chloro-1-[[2-(trimethylsilanyl)ethoxy]methyl]-benzimidazole

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

According to Scheme A, a mixture of NaH (60% dispersion in oil, 0.40 g, 9.8 mmol) and THF (10 mL) was cooled to 0° C., then solid 2-chlorobenzoimidazole (1.0 g, 6.5 mmol) was added portion wise over 10 min. The resulting mixture was stirred at 0° C. for 1 h, then 2-(trimethylsilyl)-ethoxymethyl chloride (1.5 mL, 8.5 mmol) was added. The reaction mixture was allowed to warm to 23° C. and was stirred 16 h. The mixture was carefully poured over ice (200 g) and then was extracted with Et2O (3×100 mL). The combined organic extracts were dried, filtered, and concentrated. The residue was purified (FCC) (1:99 to 15:85 EtOAc/hexanes) to yield the titled compound, which has been previously described (WO 2005/012296, Janssen Pharmaceutica N.V., Example 7).

Workup

  1. temperatureto warm to 23° C.
  2. stirringwas stirred 16 h
  3. extractionwas extracted with Et2O (3×100 mL)
  4. customThe combined organic extracts were dried
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified (FCC) (1:99 to 15:85 EtOAc/hexanes)

Sources & evidence

ORD record
ord-927b9ff1368b4a4490b875f00ce6cc74
Source dataset
uspto-grants-2014_10
Patent number
US08865713B2

Reaction notes

Loading…