Potassium Carbonate → Indole

HRID 582549Notes

Reaction equation

HRID 582549 reaction equation
CO[CH:3](OC)[CH2:4][CH2:5][CH2:6][CH2:7][N:8]1[CH2:13][CH2:12]N(C(OC(C)(C)C)=O)CC1.[C:23]([O-])([O-])=O.[K+].[K+]>S(=O)(=O)(O)O>[NH:8]1[C:7]2[C:6](=[CH:5][CH:4]=[CH:3][CH:23]=2)[CH:12]=[CH:13]1

Participants

4

Reactant 2

HCID 11430Potassium CarbonateHCID 10829224HCID 10829224, compound2×

Product 1

HCID 798IndoleYield 44%

Reagents, catalysts & solvents 1

HCID 1118Sulfuric AcidSolvent

Procedure

A mixture of Intermediate 1 (5.0 g, 28.6 mmol) and 5-[4-(tert-butyloxycarbonyl)piperazin-1-yl]pentanal dimethylacetal (9.03 g, 28.6 mmol) in 4% sulphuric acid (150 ml) was heated at reflux for 48 h. The solution was cooled in an ice-bath, basified with solid K2CO3 and extracted with butan-1-ol (×3). The solvent was removed under vacuum and azeotroped with hexane (×2). The crude product was purified by chromatography on silica gel eluting with CH2Cl2 /MeOH/NH3 (30:8:1) to give the title-indole (3.9 g, 44%). The 3.5 hydrogen oxalate salt was prepared using 200 mg of free base: mp 90-92° C. (Found: C, 45.97; H, 4.76; N, 13.77. C17H22N6.3.5(C2H2O4) requires C, 46.08; H, 4.76; N, 13.43%); δ(360 MHz, D2O) 2.12-2.24 (2H, m, CH2); 2.93 (2H, t, J=7 Hz, CH2); 3.46-3.76 (8H, m, 4 of CH2); 7.37 (1H, dd, J=1.9 and 8.7 Hz, Ar--H); 7.39 (1H, s, Ar--H); 7.66 (1H, d, J=8.7, Ar--H); 7.82 (1H, d, J=1.9 Hz, Ar--H); 9.13 (2H, s, Triazole-H).

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 48 h
  3. temperatureThe solution was cooled in an ice-bath
  4. extractionextracted with butan-1-ol (×3)
  5. customThe solvent was removed under vacuum
  6. customazeotroped with hexane (×2)
  7. customThe crude product was purified by chromatography on silica gel eluting with CH2Cl2 /MeOH/NH3 (30:8:1)

Sources & evidence

ORD record
ord-f5c3b1cd58bc498595ad45db03d0a0f2
Source dataset
uspto-grants-1999_07
Patent number
US05925638

Reaction notes

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