Indole → 3-(1,4-Dioxaspiro[4.5]dec-7-en-8-yl)-1H-indole

HRID 1410520Notes

Reaction equation

HRID 1410520 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.[CH2:10]1[O:20][C:13]2([CH2:18][CH2:17][C:16](=O)[CH2:15][CH2:14]2)[O:12][CH2:11]1.[OH-].[K+]>CO>[O:12]1[C:13]2([CH2:18][CH2:17][C:16]([C:3]3[C:4]4[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=4)[NH:1][CH:2]=3)=[CH:15][CH2:14]2)[O:20][CH2:10][CH2:11]1

Participants

5

Reactant 3

HCID 798IndoleHCID 14797Potassium HydroxideHCID 5674151,4-Dioxaspiro[4.5]decan-8-one

Product 1

HCID 27638573-(1,4-Dioxaspiro[4.5]dec-7-en-8-yl)-1H-indole

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
70 °C

Procedure

To a 2-L three-neck round bottom flask equipped with an overhead stirrer, heating mantel, temperature probe and reflux condenser was added indole (100.0 g, 0.836 mol), 1,4-cyclohexanedione monoethylene ketal (175.10 g, 1.09 mol, 1.3 eq) and methanol (221 mL). To this stirred solution was added KOH pellets (31.5 g, 0.48 mol) all at once and the reaction was heated to 70° C. for 4 hrs. The reaction was judged complete by HPLC. The resulting suspension was filtered, washed with MeOH (150 mL), followed by washing the solid with ethanol (2×150 mL). The product was further dried in a vacuum oven at 60° C. for 30 mins to remove residual solvent and obtain the title compound. 1H NMR (400 MHz, CHLOROFORM-d) δ: 7.97-8.16 (m, 1H), 7.90 (d, J=8.1 Hz, 1H), 7.35 (d, J=7.8 Hz, 1H), 7.05-7.23 (m, 3H), 6.05-6.22 (m, 1H), 3.95-4.12 (m, 4H), 2.72 (ddd, J=1.6, 4.6, 8.4 Hz, 2H), 2.45-2.61 (m, 2H), 1.97 (t, J=6.6 Hz, 2H); mp: 190.7-193.1; Elemental anal calc for C16H17NO2: C, 75.27; H, 6.71; N, 5.49. Found: C, 74.93; H, 6.73; N, 5.37; KF: <0.1.

Workup

  1. customTo a 2-L three-neck round bottom flask equipped with an overhead stirrer
  2. temperatureheating mantel, temperature probe
  3. temperaturereflux condenser
  4. filtrationThe resulting suspension was filtered
  5. washwashed with MeOH (150 mL)
  6. washby washing the solid with ethanol (2×150 mL)
  7. customThe product was further dried in a vacuum oven at 60° C. for 30 mins
  8. customto remove residual solvent

Sources & evidence

ORD record
ord-e9e9dd10275b4437be320399fa0c1925
Source dataset
uspto-grants-2014_12
Patent number
US08921559B2

Reaction notes

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