Indole → HCID 18518643, compound

HRID 1369118Notes

Reaction equation

HRID 1369118 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.[Li]CCCC.[Li]C(C)(C)C.[CH2:20]([N:22]([CH2:37][CH3:38])[CH2:23][CH2:24][N:25]1[C:35]2[C:30](=[C:31]([Br:36])[CH:32]=[CH:33][CH:34]=2)[C:28](=[O:29])[C:26]1=[O:27])[CH3:21].[NH4+].[Cl-]>C1COCC1.O>[CH2:37]([N:22]([CH2:20][CH3:21])[CH2:23][CH2:24][N:25]1[C:35]2[C:30](=[C:31]([Br:36])[CH:32]=[CH:33][CH:34]=2)[C:28]([OH:29])([C:2]2[NH:1][C:9]3[C:4]([CH:3]=2)=[CH:5][CH:6]=[CH:7][CH:8]=3)[C:26]1=[O:27])[CH3:38]

Participants

8

Reactant 5

HCID 798IndoleHCID 25517Ammonium ChlorideHCID 10958318HCID 10958318, compoundHCID 178418306HCID 178418306, compoundHCID 178418339Butyllithium

Product 1

HCID 18518643HCID 18518643, compoundYield 29%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×

Procedure

To indole (39.7 mg, 1.1 eq) in anhydrous THF (2 mL) under a nitrogen atmosphere and with stirring was added n-BuLi (0.22 mL, 1.1 eq, 1.53 M in hexanes) at −78° C. (bath temperature). Stirring was continued for 1 hour after which CO2 (g) was bubbled through the solution for ca. 30 minutes. The reaction mixture was then allowed to warm to room temperature and stirred at room temperature for a further 30 minutes. The solvent was removed in vacuo to give a white/light yellow solid which was left under vacuum (10 mmHg) for 17 hours. To the thus dried solid under a nitrogen atmosphere was added anhydrous THF (2 mL). The resulting clear solution was cooled to −78° C. (bath temperature) and t-BuLi (0.20 mL, 1.1 eq, 1.7 M in pentane) added dropwise. The colourless solution was stirred for 1 hour and 1-(2-diethylaminoethyl)-4-bromoisatin (100.0 mg, 3.08×10−4 mol) in anhydrous THF (2 mL) was added dropwise. The resulting red coloured solution was stirred at −40° C. for 7.5 hours. To the solution was added H2O (1.5 mL) and the mixture allowed to warm to room temperature. Saturated aqueous NH4Cl (1.5 mL) was then added. The mixture was extracted with EtOAc and the combined extracts were dried (anhydrous Na2SO4). After filtration the solvent was removed in vacuo. Purification was carried out by column chromatography (silica gel, eluting 1% to 1.5% MeOH in CHCl3) to give the title compound as a red oil (39.4 mg, 29%).

Workup

  1. customafter which CO2 (g) was bubbled through the solution for ca. 30 minutes
  2. stirringstirred at room temperature for a further 30 minutes
  3. customThe solvent was removed in vacuo
  4. customto give a white/light yellow solid which
  5. waitwas left under vacuum (10 mmHg) for 17 hours
  6. additionadded dropwise
  7. stirringThe colourless solution was stirred for 1 hour
  8. stirringwas stirred at −40° C. for 7.5 hours
  9. temperatureto warm to room temperature
  10. extractionThe mixture was extracted with EtOAc
  11. dry with materialthe combined extracts were dried (anhydrous Na2SO4)
  12. filtrationAfter filtration the solvent
  13. customwas removed in vacuo
  14. customPurification
  15. washwas carried out by column chromatography (silica gel, eluting 1% to 1.5% MeOH in CHCl3)

Sources & evidence

ORD record
ord-f2296227926e4a348b22b6d640f309b9
Source dataset
uspto-grants-2003_06
Patent number
US06576656B1

Reaction notes

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