Iodoethane → 1-(2-Benzimidazol-2-ylethyl)-3-ethoxybenzene

HRID 537320Notes

Reaction equation

HRID 537320 reaction equation
[N:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[NH:3][C:2]=1[CH2:10][CH2:11][C:12]1[CH:13]=[C:14]([OH:18])[CH:15]=[CH:16][CH:17]=1.C([O-])([O-])=O.[K+].[K+].[CH2:25](I)[CH3:26].C(C1C2NC(CC)=NC=2C=CC=1)C>CN(C=O)C>[N:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[NH:3][C:2]=1[CH2:10][CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([O:18][CH2:25][CH3:26])[CH:13]=1

Participants

6

Reactant 4

HCID 6340IodoethaneHCID 11430Potassium CarbonateHCID 866892943-(2-Benzimidazol-2-ylethyl)phenolHCID 178437416HCID 178437416, compound

Product 1

HCID 866892951-(2-Benzimidazol-2-ylethyl)-3-ethoxybenzeneYield 38.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A 100 mL flask fitted with a stir-bar and septum with an Ar inlet was charged with benzimidazole 69 (2.00 g, 8.39 mmol), K2CO3 (1.74 g, 12.6 mmol), and DMF (20 mL). Ethyl iodide (1.44 g, 0.74 mL, 9.23 mmol) was added, and the mixture stirred at rt overnight. Analysis by HPLC showed a mixture of approximately 1:3:2 starting material:product:diethylbenzimidazole. The solids were filtered off and rinsed with EtOAc (60 mL). The filtrate was washed with saturated aqueous NH4Cl (2×50 mL), H2O (2×50 mL), 1% aqueous LiOH (4×50 mL), and brine (25 mL). The solution was filtered through phase separation paper and concentrated to 1.85 g of a yellow oil. The crude oil was chromatographed on silica gel with the product eluting with 25-35% EtOAc in hexanes. The product fractions were concentrated in vacuo to a white solid that was collected with hexanes. The material was dried to give 855 mg of 70 as a white solid (38%). 1H NMR (60 MHz, CDCl3): δ 7.8-7.5 (m, 2H), 7.5-7.0 (m, 3H), 6.9-6.6 (m, 3H), 3.8 (qt, 2H), 3.3-2.9 (m, 4H), 1.3 (t, 3H) ppm. HPLC analysis (15:10:75 H2O:A1:MeOH) showed a purity of 99% with a retention time of 3.6 min.

Workup

  1. customA 100 mL flask fitted with a stir-bar
  2. additiona mixture of approximately 1:3:2 starting material
  3. filtrationThe solids were filtered off
  4. washrinsed with EtOAc (60 mL)
  5. washThe filtrate was washed with saturated aqueous NH4Cl (2×50 mL), H2O (2×50 mL), 1% aqueous LiOH (4×50 mL), and brine (25 mL)
  6. filtrationThe solution was filtered through phase separation paper
  7. concentrationconcentrated to 1.85 g of a yellow oil
  8. customThe crude oil was chromatographed on silica gel with the product
  9. washeluting with 25-35% EtOAc in hexanes
  10. concentrationThe product fractions were concentrated in vacuo to a white solid
  11. customthat was collected with hexanes
  12. customThe material was dried

Sources & evidence

ORD record
ord-4a19f2af02a94b788471fe33168de0e0
Source dataset
uspto-grants-2014_10
Patent number
US08859780B2

Reaction notes

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