Methyl iodide → 2-Ethyl-8-(4-phenyl-2-pyridinyl)benzofuro[2,3-b]pyridine

HRID 1844922Notes

Reaction equation

HRID 1844922 reaction equation
[CH3:1][C:2]1[N:7]=[C:6]2[O:8][C:9]3[C:14]([C:15]4[CH:20]=[C:19]([C:21]5[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=5)[CH:18]=[CH:17][N:16]=4)=[CH:13][CH:12]=[CH:11][C:10]=3[C:5]2=[CH:4][CH:3]=1.[CH:27]([N-]C(C)C)(C)C.[Li+].IC>C1COCC1>[CH2:1]([C:2]1[N:7]=[C:6]2[O:8][C:9]3[C:14]([C:15]4[CH:20]=[C:19]([C:21]5[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=5)[CH:18]=[CH:17][N:16]=4)=[CH:13][CH:12]=[CH:11][C:10]=3[C:5]2=[CH:4][CH:3]=1)[CH3:27]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 2724682Lithium diisopropylamideHCID 901214912-Methyl-8-(4-phenyl-2-pyridinyl)benzofuro[2,3-b]pyridine

Product 1

HCID 901216022-Ethyl-8-(4-phenyl-2-pyridinyl)benzofuro[2,3-b]pyridineYield 93%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-78 °C

Procedure

2-methyl-8-(4-phenylpyridin-2-yl)benzofuro[2,3-b]pyridine (5.3 g, 15.76 mmol) was dissolved in 130 mL of THF. This solution was cooled in a dry ice bath to −78° C. Lithium diisopropylamide in THF (9.85 mL, 19.69 mmol) was added dropwise to the reaction mixture over a 10 minute period maintaining the temperature below −73° C. The reaction mixture was stirred at −78° C. for 2 hours. Iodomethane (3.35 g, 23.63 mmol) was dissolved in 20 mL of THF then was added dropwise via syringe to the cold reaction mixture. Stirring was continued as the reaction mixture gradually warmed 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 5-8% ethyl acetate/DCM. The main set of product fractions were combined and concentrated under vacuum yielding 2-ethyl-8-(4-phenylpyridin-2-yl)benzofuro[2,3-b]pyridine (5.15 g, 14.70 mmol, 93% yield)

Workup

  1. temperaturemaintaining the temperature below −73° C
  2. additionthen was added dropwise via syringe to the cold reaction mixture
  3. stirringStirring
  4. temperaturegradually warmed to room temperature overnight
  5. customThe reaction mixture was quenched with aqueous ammonium chloride
  6. extractionthen was extracted 2×300 mL ethyl acetate
  7. washwere washed with aqueous LiCl
  8. dry with materialthen were dried over magnesium sulfate
  9. filtrationThese organics were then filtered
  10. concentrationconcentrated under vacuum
  11. dissolutionThe crude residue was dissolved in DCM
  12. washThe column was eluted with 5-8% ethyl acetate/DCM
  13. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-d7459888face4cb7bbe43f4e7b9c5f55
Source dataset
uspto-grants-2015_02
Patent number
US08946697B1

Reaction notes

Loading…