Sodium Iodide → Indole

HRID 1602100Notes

Reaction equation

HRID 1602100 reaction equation
F[C:2]1[CH:7]=[CH:6][C:5]([CH:8]([CH3:11])CBr)=[CH:4][CH:3]=1.C([N:14](CC)CC)C.[I-].[Na+]>CN(C=O)C>[NH:14]1[C:6]2[C:5](=[CH:4][CH:3]=[CH:2][CH:7]=2)[CH:8]=[CH:11]1

Participants

5

Reactant 3

HCID 5238Sodium IodideHCID 8471TriethylamineHCID 2203822490561-73-2

Product 1

HCID 798IndoleYield 101.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of Intermediate 3 (0.31 g, 1.0 mmol), 2-(4-fluorophenyl)propyl bromide (0.228 g, 1.05 mmol), triethylamine (0.202 g, 2.0 mmol) and sodium iodide (0.165 g, 1.1 mmol), in DMF (20 ml) was heated at 90° C., with stirring, for 16 h. The mixture was cooled to room temperature and partitioned between dichloromethane and water. The CH2Cl2 layer was separated, dried (Na2SO4) and evaporated under vacuum. The crude product was chromatographed through silica gel eluting with CH2Cl2 /MeOH/NH3 (90:10:1) to give the title-indole (0.125 g, 28%). The 3.0 hydrogen oxalate monohydrate salt was prepared, mp 203-205° C., (Found: C, 52.11; H, 5.60; N, 11.45. C26H31N6F. 3.0 (C2H2O4) 1.0H2O requires C, 52.31; H, 5.35; N, 11.44%), δ(360 MHz, D6 -DMSO) 1.17 (3H, d, J=6.8 Hz, Me), 1.92-2.06 (2H, m, CH2), 2.44-3.26 (15H, m, 7 of CH2 and CH), 7.08-7.13 (2H, m, Ar--H), 7.26-7.33 (4H, m, Ar--H), 7.50 (1H, d, J=8.6 Hz, Ar--H), 7.78 (1H, d, J=1.5 Hz, Ar--H), 9.01 (2H, s, Ar--H), 11.16 (1H, s, NH).

Workup

  1. custompartitioned between dichloromethane and water
  2. customThe CH2Cl2 layer was separated
  3. dry with materialdried (Na2SO4)
  4. customevaporated under vacuum
  5. customThe crude product was chromatographed through silica gel eluting with CH2Cl2 /MeOH/NH3 (90:10:1)

Sources & evidence

ORD record
ord-d123d2cdbdc64b8593ad7432e3952f44
Source dataset
uspto-grants-1999_11
Patent number
US05981529

Reaction notes

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