Methyl iodide → HCID 57190276, compound

HRID 439851Notes

Reaction equation

HRID 439851 reaction equation
[CH:1]([C:4]1[CH:12]=[CH:11][C:10]2[NH:9][CH:8]3[C:13]4[C:18]([CH2:19][CH:7]3[C:6]=2[CH:5]=1)=[CH:17][CH:16]=[CH:15][CH:14]=4)([CH3:3])[CH3:2].[CH2:20]([Li])CCC.IC>O1CCCC1>[CH3:20][C@@:8]12[C:13]3[C:18](=[CH:17][CH:16]=[CH:15][CH:14]=3)[CH2:19][C@@H:7]1[C:6]1[CH:5]=[C:4]([CH:1]([CH3:3])[CH3:2])[CH:12]=[CH:11][C:10]=1[NH:9]2

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 4113271HCID 4113271, compoundHCID 178418339Butyllithium

Product 1

HCID 57190276HCID 57190276, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

Under an inert atmosphere, a flame-dried flash was charged with 4b,5,9b,10-tetrahydro-8-isopropylindeno[1,2-b]indole (1.49 g 5.98 mmol) and dry tetrahydrofuran (THF, 20 cm3). The solution was cooled to -78° C., and a solution of n-butyllithium in hexanes (4.0 cm3 of 1.6M solution) added dropwise. The reaction was warmed to room temperature, and dry CO2 gas bubbled through until the colour of the anion had dispersed. The solvent and excess CO2 were carefully removed at a vacuum pump, the resulting solid re-dissolved in dry THF (20 cm3) and cooled to -78° C. A further equivalent of n-butyllithium was added, and the reaction stirred at -20° C. for 30 minutes. Iodomethane (0.4 cm3, 1 eq) was added at -78° C., and the reaction warmed to room temperature and stirred for 3 hours. The solvents were removed at the water pump, and 2N HCl solution (20 cm3) added. After 20 minutes, the solution was basified with solid sodium carbonate, and extracted into ethyl acetate. The organic extract was washed with brine, dried (Na2SO4) and concentrated in vacuo. The product was purified by flash chromatography as an unstable pale yellow oil. Yield: 1.01 g, 64%. 1H NMR (CDCl3) δ: 7.30-7.15 (4H, m), 7.00 (1H, s), 6.85 (1H, d, J=7.9 Hz), 6.49 (1H, d, J=7.9 Hz), 4.0 (1H, br), 3.73 (1H, d, J=8.1 Hz), 3.49 (1H, dd, J=16.1, 8.2 Hz), 3.16 (1H, d, J=16.1 Hz), 2.79 (1H, septet, J=6.8 Hz), 1.61 (3H, s), 1.19 (6H, d, J=6.8 Hz).

Workup

  1. temperatureThe reaction was warmed to room temperature
  2. customdry CO2 gas bubbled through until the colour of the anion
  3. additionhad dispersed
  4. customThe solvent and excess CO2 were carefully removed at a vacuum pump
  5. dissolutionthe resulting solid re-dissolved in dry THF (20 cm3)
  6. temperaturecooled to -78° C
  7. additionA further equivalent of n-butyllithium was added
  8. temperaturethe reaction warmed to room temperature
  9. stirringstirred for 3 hours
  10. customThe solvents were removed at the water pump, and 2N HCl solution (20 cm3)
  11. additionadded
  12. waitAfter 20 minutes
  13. extractionextracted into ethyl acetate
  14. extractionThe organic extract
  15. washwas washed with brine
  16. dry with materialdried (Na2SO4)
  17. concentrationconcentrated in vacuo
  18. customThe product was purified by flash chromatography as an unstable pale yellow oil

Sources & evidence

ORD record
ord-01d29ed230554043aa637b6d1e0e3310
Source dataset
uspto-grants-1996_05
Patent number
US05516788

Reaction notes

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