1,2-Dichloroethane → 2-[(4-benzylpiperidin-1-yl)methyl]-1H-benzimidazole

HRID 1016429Notes

Reaction equation

HRID 1016429 reaction equation
[CH2:1]([CH:8]1[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C[Si](C)(C)CCOC[N:20]1[C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][C:23]=2[N:22]=[C:21]1[CH:29]=O.ClCCCl.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)(Cl)Cl.C([O-])([O-])=O.[Na+].[Na+]>[CH2:1]([CH:8]1[CH2:13][CH2:12][N:11]([CH2:29][C:21]2[NH:22][C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=3[N:20]=2)[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 111,2-DichloroethaneHCID 317384-BenzylpiperidineHCID 5049666Sodium triacetoxyborohydrideHCID 120171281-(2-Trimethylsilylethoxymethyl)-2-formyl-benzimidazole

Product 1

HCID 6676742-[(4-benzylpiperidin-1-yl)methyl]-1H-benzimidazoleYield 144.8%

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 10340Sodium CarbonateSolvent

Procedure

A mixture of 0.5 g of 4-benzyl-piperidine, 0.5 g of 1-(2-trimethylsilylethoxymethyl)-1H-benzoimidazole-2-carbaldehyde, 5 mL of 1,2-dichloroethane and 0.5 g of sodium triacetoxyborohydride was stirred at room temperature for 48 h. The reaction mixture was diluted with 50 mL chloroform and 10 mL saturated aqueous Na2CO3 and the layers separated. The aqueous layer was extracted with 2×25 mL of chloroform and the combined organic layers dried over magnesium sulfate and concentrated under reduced pressure. The crude SEM ether was heated to reflux in 50 mL of ethanol containing 5 mL of 3N HCl for 2 h, cooled, concentrated and partitioned between 10 mL of saturated aqueous sodium carbonate and 3×25 mL of chloroform. The chloroform extracts were dried over magnesium sulfate and concentrated. Purification by chromatography eluting with 90:10 CHCl3: MeOH gave 0.8 g of 2-[4-benzyl-piperidin-1-ylmethyl]-1H-benzimidazole: MS (m+1)=: 1H NMR (400MHz, CDCl3).

Workup

  1. customthe layers separated
  2. extractionThe aqueous layer was extracted with 2×25 mL of chloroform
  3. dry with materialthe combined organic layers dried over magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. temperatureThe crude SEM ether was heated
  6. temperatureto reflux in 50 mL of ethanol containing 5 mL of 3N HCl for 2 h
  7. temperaturecooled
  8. concentrationconcentrated
  9. custompartitioned between 10 mL of saturated aqueous sodium carbonate and 3×25 mL of chloroform
  10. dry with materialThe chloroform extracts were dried over magnesium sulfate
  11. concentrationconcentrated
  12. customPurification by chromatography
  13. washeluting with 90:10 CHCl3

Sources & evidence

ORD record
ord-542d80c6bd254f2a9d3f7fef6a1fb71d
Source dataset
uspto-grants-2002_11
Patent number
US06476041B1

Reaction notes

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