Methyl iodide → 2-Isopropyl-8-(4-phenylpyridin-2-yl)benzofuro[2,3-b]pyridine

HRID 1844923Notes

Reaction equation

HRID 1844923 reaction equation
[CH2:1]([C:3]1[N:8]=[C:7]2[O:9][C:10]3[C:15]([C:16]4[CH:21]=[C:20]([C:22]5[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=5)[CH:19]=[CH:18][N:17]=4)=[CH:14][CH:13]=[CH:12][C:11]=3[C:6]2=[CH:5][CH:4]=1)[CH3:2].[CH:28]([N-]C(C)C)(C)C.[Li+].IC>C1COCC1>[CH:1]([C:3]1[N:8]=[C:7]2[O:9][C:10]3[C:15]([C:16]4[CH:21]=[C:20]([C:22]5[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=5)[CH:19]=[CH:18][N:17]=4)=[CH:14][CH:13]=[CH:12][C:11]=3[C:6]2=[CH:5][CH:4]=1)([CH3:28])[CH3:2]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 2724682Lithium diisopropylamideHCID 901216022-Ethyl-8-(4-phenyl-2-pyridinyl)benzofuro[2,3-b]pyridine

Product 1

HCID 901215622-Isopropyl-8-(4-phenylpyridin-2-yl)benzofuro[2,3-b]pyridineYield 77%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-78 °C

Procedure

2-ethyl-8-(4-phenylpyridin-2-yl)benzofuro[2,3-b]pyridine (5.15 g, 14.70 mmol) was charged into the reaction mixture with 120 mL of THF. This mixture was cooled to −78° C. Lithium diisopropylamide in THF (9.19 mL, 18.37 mmol) was added dropwise to the cooled reaction mixture over a 10 minute period. The reaction mixture was then stirred for 2 hours at −78° C. Iodomethane (3.13 g, 22.05 mmol) was then dissolved in 10 mL of THF. This solution was then added via syringe to the cold reaction mixture. Stirring was continued as the reaction mixture was allowed to gradually warm to room temperature overnight. The reaction mixture was quenched with aqueous ammonium chloride then was extracted 2×300 mL ethyl acetate. The organics were combined, were washed with aqueous LiCl then were dried over magnesium sulfate. These organics were then filtered and concentrated under vacuum. The crude residue was dissolved in DCM and was loaded onto a silica gel column. The column was eluted with 3-4% ethyl acetate/DCM. Clean product fractions were combined and solvents were evaporated yielding 2-isopropyl-8-(4-phenylpyridin-2-yl)benzofuro[2,3-b]pyridine (4.1 g, 11.25 mmol, 77% yield).

Workup

  1. additionThis solution was then added via syringe to the cold reaction mixture
  2. stirringStirring
  3. temperatureto gradually warm to room temperature overnight
  4. customThe reaction mixture was quenched with aqueous ammonium chloride
  5. extractionthen was extracted 2×300 mL ethyl acetate
  6. washwere washed with aqueous LiCl
  7. dry with materialthen were dried over magnesium sulfate
  8. filtrationThese organics were then filtered
  9. concentrationconcentrated under vacuum
  10. dissolutionThe crude residue was dissolved in DCM
  11. washThe column was eluted with 3-4% ethyl acetate/DCM
  12. customsolvents were evaporated

Sources & evidence

ORD record
ord-f69e03916d014de2aa1ae7b735e5ef74
Source dataset
uspto-grants-2015_02
Patent number
US08946697B1

Reaction notes

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