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

HRID 1410521Notes

Reaction equation

HRID 1410521 reaction equation
[O:1]1[C:5]2([CH2:10][CH2:9][C:8]([C:11]3[C:19]4[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=4)[NH:13][CH:12]=3)=[CH:7][CH2:6]2)[O:4][CH2:3][CH2:2]1.[H][H]>[Pd].C1COCC1>[O:4]1[C:5]2([CH2:6][CH2:7][CH:8]([C:11]3[C:19]4[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=4)[NH:13][CH:12]=3)[CH2:9][CH2:10]2)[O:1][CH2:2][CH2:3]1

Participants

5

Reactant 2

HCID 27638573-(1,4-Dioxaspiro[4.5]dec-7-en-8-yl)-1H-indoleHCID 178418361HCID 178418361, compound2×

Product 1

HCID 108487533-(1,4-dioxaspiro[4.5]decan-8-yl)-1H-indole

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

To a 2-L PAAR hydrogenation bottle was charged Pd/C (10%, 11.06 g) and part of THF (1.11 L). Solid 3-(1,4-dioxaspiro[4.5]dec-7-en-8-yl)-1H-indole (as prepared in the previous step, 221.1 g) was added along with the rest of the THF. The bottle was connected to the PAAR shaker, cycled through vacuum/nitrogen (3×), vacuum/hydrogen (3×) and the 45 psi hydrogen was applied with shaking Over the course of 4 hrs, the pressure dropped and was recharged until 45 psi was maintained. The reaction was complete by LCMS. The catalyst was filtered using celite/glass fiber filter, and the reaction was evaporated, but not to complete dryness. Denatured EtOH (250 mL) was added, the reaction concentrated, but again not to dryness. EtOH (1050 mL) was added, the contents heated to boiling, which dissolved nearly all the material. The mixture was allowed to come to ambient temperature with stirring and the product precipitated. After coming to ambient temperature, the suspension was chilled in a refrigerator for 3 hrs, and the product was filtered, and washed with ice-cold EtOH (250 mL) to obtain the title compound. 1H NMR (400 MHz, CHLOROFORM-d) δ: 7.79-8.04 (m, 1H), 7.66 (d, J=7.3 Hz, 1H), 7.36 (d, J=8.1 Hz, 1H), 7.18 (s, 1H), 7.12 (d, J=6.8 Hz, 1H), 6.99 (d, J=2.2 Hz, 1H), 4.00 (s, 4H), 2.74-3.03 (m, 1H), 2.09 (br. s., 2H), 1.66-1.96 (m, 6H). 13C NMR (101 MHz, CHLOROFORM-d): 136.4, 126.8, 121.9, 119.3, 111.1, 108.9, 77.2, 64.3, 35.1, 34.1, 31.0.

Workup

  1. additionthe pressure dropped
  2. temperaturewas maintained
  3. filtrationThe catalyst was filtered
  4. filtrationfilter
  5. customthe reaction was evaporated
  6. additionDenatured EtOH (250 mL) was added
  7. concentrationthe reaction concentrated
  8. additionEtOH (1050 mL) was added
  9. temperaturethe contents heated to boiling, which
  10. dissolutiondissolved nearly all the material
  11. customto come to ambient temperature
  12. stirringwith stirring
  13. customthe product precipitated
  14. customAfter coming to ambient temperature
  15. temperaturethe suspension was chilled in a refrigerator for 3 hrs
  16. filtrationthe product was filtered
  17. washwashed with ice-cold EtOH (250 mL)

Sources & evidence

ORD record
ord-c4ceb98a34484ddab117a3f6b9462e17
Source dataset
uspto-grants-2014_12
Patent number
US08921559B2

Reaction notes

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