Iodine → methyl 3-iodo-1H-indole-5-carboxylate

HRID 634185Notes

Reaction equation

HRID 634185 reaction equation
[I:1]I.[NH:3]1[C:11]2[C:6](=[CH:7][C:8]([C:12]([O:14][CH3:15])=[O:13])=[CH:9][CH:10]=2)[CH:5]=[CH:4]1.C(=O)([O-])[O-].[K+].[K+].S(=O)(O)[O-].[Na+]>CN(C=O)C.O>[I:1][C:5]1[C:6]2[C:11](=[CH:10][CH:9]=[C:8]([C:12]([O:14][CH3:15])=[O:13])[CH:7]=2)[NH:3][CH:4]=1

Participants

7

Reactant 4

HCID 807IodineHCID 11430Potassium CarbonateHCID 2737635methyl 1H-indole-5-carboxylateHCID 23665763Sodium Bisulfite

Product 1

HCID 50989132methyl 3-iodo-1H-indole-5-carboxylateYield 90%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Conditions

Temperature
25 °C

Procedure

A brown solution of I2 (3.98 g, 15.70 mmol) in DMF (4.0 mL) was added dropwise over 5 min to a yellow-brown suspension of methyl 1H-indole-5-carboxylate (Aldrich, St. Louis, Mo.; 2.5 g, 14.27 mmol) and potassium carbonate (3.96 g, 28.7 mmol) in DMF (14.0 mL), and the resulting mixture was stirred at 25° C. for 16 h. The mixture was added to a mixture of ice (10 g), H2O (200 mL), and sodium bisulfite (2.228 g, 21.41 mmol). The resulting mixture was extracted with DCM (2×200 mL), and the combined organic extracts were dried over sodium sulfate, filtered, and concentrated in vacuo to provide methyl 3-iodo-1H-indole-5-carboxylate (3.87 g, 12.85 mmol, 90%) as a brown solid: MS (ESI, pos. ion) m/z: 301.9 (M+1). 1H NMR (400 MHz, CDCl3) δ ppm 8.22 (s, 1H), 8.00-8.03 (m, 1H), 7.96 (dd, J=8.6, 1.4 Hz, 1H), 7.39 (d, J=8.8 Hz, 1H), 7.37 (d, J=2.3 Hz, 1H), 3.96 (s, 3H).

Workup

  1. extractionThe resulting mixture was extracted with DCM (2×200 mL)
  2. dry with materialthe combined organic extracts were dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-2fb28defe9894b6bb201854cbc1c8310
Source dataset
uspto-grants-2016_04
Patent number
US09321756B2

Reaction notes

Loading…