4-iodo-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazole → 7-Chloro-2-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-4-yl)thieno[3,2-b]pyridine

HRID 500786Notes

Reaction equation

HRID 500786 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[CH:8]=[CH:9][S:10][C:3]=12.[Li]CCCC.I[C:17]1[N:18]=[CH:19][N:20]([CH2:22][O:23][CH2:24][CH2:25][Si:26]([CH3:29])([CH3:28])[CH3:27])[CH:21]=1>C1COCC1.[Cl-].[Cl-].[Zn+2].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[CH:8]=[C:9]([C:17]3[N:18]=[CH:19][N:20]([CH2:22][O:23][CH2:24][CH2:25][Si:26]([CH3:29])([CH3:28])[CH3:27])[CH:21]=3)[S:10][C:3]=12

Participants

7

Reactant 3

HCID 110672924-iodo-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazoleHCID 112752517-Chlorothieno[3,2-b]pyridineHCID 178418339Butyllithium

Product 1

HCID 594244277-Chloro-2-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-4-yl)thieno[3,2-b]pyridineYield 73.2%

Reagents, catalysts & solvents 3

HCID 3007855ZincchlorideCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a solution of 2 (9.4 g, 56.0 mmol) in THF (150 ml) at −78° C. was added n-BuLi (28 ml, 70.0 mmol, 2.5 M soln in hexanes) and the reaction mixture was stirred at −78° C. for 45 mins. A solution of ZnCl2 (140 ml, 70.0 mmol, 0.5M in THF) was added and the reaction mixture was warmed to room temperature. To the warmed mixture a solution of 4-iodo-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazole [Carl J. Lovey et al, Tetrahedron Lett., 2004, 45(28), 5529-5532] (9.0 g, 28.0 mmol) and Pd(PPh3)4 (2.5 g, 2.1 mmol) in THF added. The reaction mixture was heated to reflux for 3 hrs, cooled to room temperature, quenched with aqueous ammonium hydroxide and made neutral with aqueous HCl. The neutral solution was extracted with EtOAc, the organic phase was collected, dried over anhydrous sodium sulfate and filtered. The filtrate was evaporated under reduced pressure and the residue was purified by column chromatography (eluent MeOH-EtOAc, 1:20) to afford the title compound 91 (7.5 g, 73% yield) as a brown oil. MS (m/z) 366.0/368.0 (M+H).

Workup

  1. temperaturethe reaction mixture was warmed to room temperature
  2. temperatureThe reaction mixture was heated
  3. temperatureto reflux for 3 hrs
  4. temperaturecooled to room temperature
  5. customquenched with aqueous ammonium hydroxide
  6. extractionThe neutral solution was extracted with EtOAc
  7. customthe organic phase was collected
  8. dry with materialdried over anhydrous sodium sulfate
  9. filtrationfiltered
  10. customThe filtrate was evaporated under reduced pressure
  11. customthe residue was purified by column chromatography (eluent MeOH-EtOAc, 1:20)

Sources & evidence

ORD record
ord-c92e7d3a4e274d708a5e2de83a2f9e1c
Source dataset
uspto-grants-2010_08
Patent number
US07772247B2

Reaction notes

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