Iodine → 5-Fluoro-3-iodo-1H-indole-2-carboxylic acid (3-hydroxy-propyl)-amide

HRID 29784Notes

Reaction equation

HRID 29784 reaction equation
[OH:1][CH2:2][CH2:3][CH2:4][NH:5][C:6]([C:8]1[NH:9][C:10]2[C:15]([CH:16]=1)=[CH:14][C:13]([F:17])=[CH:12][CH:11]=2)=[O:7].[OH-].[K+].[I:20]I>CN(C=O)C>[OH:1][CH2:2][CH2:3][CH2:4][NH:5][C:6]([C:8]1[NH:9][C:10]2[C:15]([C:16]=1[I:20])=[CH:14][C:13]([F:17])=[CH:12][CH:11]=2)=[O:7]

Participants

5

Reactant 3

HCID 807IodineHCID 14797Potassium HydroxideHCID 597892005-fluoro-1H-indole-2-carboxylic acid (3-hydroxy-propyl)-amide

Product 1

HCID 597892045-Fluoro-3-iodo-1H-indole-2-carboxylic acid (3-hydroxy-propyl)-amide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 5-fluoro-1H-indole-2-carboxylic acid (3-hydroxy-propyl)-amide, prepared as in reference 11, (4.89 g, 20.7 mmol) in DMF (100 mL) is added KOH (3.48 g, 62 mmol) and I2 (5.78 g, 22.8 mmol). It is stirred at room temperature for 1 hour and concentrated. Water is added to the residue and the mixture is acidified with HCl. The mixture is extracted with EtOAc (100 mL×2). The combined organic layers are washed with Na2S2O3 (1M, 50 mL), brine (100 mL), and dried with Na2SO4. Solvent is removed to give 5-fluoro-3-iodo-1H-indole-2-carboxylic acid (3-hydroxy-propyl)-amide; 1H NMR (DMSO-d6) δ 1.73 (quint, 2H, J=6.0 Hz), 3.39 (q, 2H, J=6.0 Hz), 3.54 (t, 2H, J=6.0 Hz), 4.54 (bs, 1H), 7.06-7.16 (m, 2H), 7.46 (dd, 1H, J1=4.4 Hz, J2=8.8 Hz), 8.00 (t, 1H, J=6.0 Hz), 12.10 (s, 1H); m/z [M++1] 363.0.

Workup

  1. concentrationconcentrated
  2. additionWater is added to the residue
  3. extractionThe mixture is extracted with EtOAc (100 mL×2)
  4. washThe combined organic layers are washed with Na2S2O3 (1M, 50 mL), brine (100 mL)
  5. dry with materialdried with Na2SO4
  6. customSolvent is removed

Sources & evidence

ORD record
ord-262d94c921a64e29a75d9b7ae45fe0f1
Source dataset
uspto-grants-2008_09
Patent number
US07423031B2

Reaction notes

Loading…