Ethanol → 8-bromo-2,3,5,10,11,11a-hexahydro-1H-indolizino[7,6-b]indole

HRID 1918492Notes

Reaction equation

HRID 1918492 reaction equation
[CH2:1]1[CH:9]2[N:4]([CH2:5][CH2:6][C:7](=O)[CH2:8]2)[CH2:3][CH2:2]1.Cl.[Br:12][C:13]1[CH:14]=[C:15]([NH:19]N)[CH:16]=[CH:17][CH:18]=1.C(O)C>Cl>[Br:12][C:13]1[CH:14]=[C:15]2[C:16]([C:6]3[CH2:5][N:4]4[CH:9]([CH2:1][CH2:2][CH2:3]4)[CH2:8][C:7]=3[NH:19]2)=[CH:17][CH:18]=1

Participants

5

Reactant 3

HCID 702EthanolHCID 337573-Bromophenylhydrazine hydrochlorideHCID 11240524Octahydroindolizin-7-one

Product 1

HCID 580923028-bromo-2,3,5,10,11,11a-hexahydro-1H-indolizino[7,6-b]indoleYield 26.6%

Reagents, catalysts & solvents 1

HCID 313Hydrochloric AcidSolvent

Procedure

Hexahydroindolizin-7(1H)-one (4.58 g, 32.9 mmol) and 3-bromophenylhydrazine hydrochloride (8.08 g, 36.2 mmol) were combined in concentrated hydrochloric acid (40 ml) and ethanol (15 ml) and heated at 105° C. for 48 h. Upon cooling, the solid was filtered off and partitioned between methylene chloride and 6 N NaOH solution. The organic layer was removed and concentrated to provide 8-bromo-2,3,5,10,11,11a-hexahydro-1H-indolizino[7,6-b]indole (2.55 g, 26%). The original filtrate was concentrated and partitioned between methylene chloride and 6 N NaOH solution. The organic layer was removed and concentrated, and the residue was purified by column chromatography (eluting with methylene chloride and a 10:1 methanol/ammonium hydroxide mixture; gradient 100% methylene chloride to 85% methylene chloride) to provide the title compound (1.31 g, 14%) as a brown solid: 1H NMR (500 MHz, DMSO-d6) δ 10.96 (s, 1H), 7.44-7.43 (d, J=1.7 Hz, 1H), 7.31-7.29 (d, J=8.4 Hz, 1H), 7.06-7.03 (dd, J=Hz, 1H), 3.79-3.76 (m, 1H), 3.22-3.17 (m, 1H), 2.91-2.85 (m, 2H), 2.79-2.74 (m, 1H), 2.64-2.59 (m, 2H), 2.38-2.31 (m, 1H), 1.81-1.70 (m, 2H), 1.68-1.66 (m, 1H); ESI MS m/z 292 [M+H]+.

Workup

  1. temperatureUpon cooling
  2. filtrationthe solid was filtered off
  3. custompartitioned between methylene chloride and 6 N NaOH solution
  4. customThe organic layer was removed
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-c0ed4ef4efaa4a6d94fdbfe94ae2de77
Source dataset
uspto-grants-2013_12
Patent number
US08618299B2

Reaction notes

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