2-Bromopropane → methyl 7-methyl-1-(1-methylethyl)-1H-indole-4-carboxylate

HRID 1476978Notes

Reaction equation

HRID 1476978 reaction equation
[CH3:1][C:2]1[C:10]2[NH:9][CH:8]=[CH:7][C:6]=2[C:5]([C:11]([O:13][CH3:14])=[O:12])=[CH:4][CH:3]=1.[H-].[Na+].I[CH:18]([CH3:20])[CH3:19].BrC(C)C>CN(C=O)C>[CH3:1][C:2]1[C:10]2[N:9]([CH:18]([CH3:20])[CH3:19])[CH:8]=[CH:7][C:6]=2[C:5]([C:11]([O:13][CH3:14])=[O:12])=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 63582-BromopropaneHCID 6362Isopropyl iodide2×HCID 24758Sodium hydride3×HCID 67465603methyl 7-methyl-1H-indole-4-carboxylate

Product 1

HCID 67468444methyl 7-methyl-1-(1-methylethyl)-1H-indole-4-carboxylateYield 43.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

A cooled (ice/water bath) solution of methyl 7-methyl-1H-indole-4-carboxylate (260 mg, 1.374 mmol) in DMF (20 mL) was added sodium hydride (43.4 mg, 1.718 mmol). After 10 minutes 2-iodopropane (0.151 mL, 1.512 mmol) was added and the reaction was stirred for 16 h. LCMS showed reaction only 10% complete. Added sodium hydride (43.4 mg, 1.718 mmol) followed by 2-iodopropane (0.151 mL, 1.512 mmol). After 2 hours LCMS showed reaction was 15% compete. Added more sodium hydride (43.4 mg, 1.718 mmol) and let stir for 5 minutes, then added more 2-bromopropane (0.142 mL, 1.512 mmol). Heated to 70° C. for 16 h. LCMS showed reaction 50% complete. Concentrated reaction mixture. Added DCM and washed with water and brine, dried over MgSO4, filtered and concentrated. The residue was purified by column chromatography (Biotage; 0% to 100% DCM:Hex; 25 g-HP-silica gel column) to give 137 mg of the title compound. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.48-1.60 (m, 6H), 2.78 (s, 3H), 3.94-4.02 (m, 3H), 5.17 (dt, J=13.20, 6.66 Hz, 1H), 6.96 (d, J=7.83 Hz, 1H), 7.28 1H, 7.40 (d, J=3.28 Hz, 1H), 7.81 (d, J=7.58 Hz, 1H). MS(ES) [M+H]+ 232.1

Workup

  1. customreaction only 10% complete
  2. waitAfter 2 hours LCMS showed
  3. customreaction
  4. stirringlet stir for 5 minutes
  5. customreaction 50% complete
  6. concentrationConcentrated
  7. customreaction mixture
  8. washAdded DCM and washed with water and brine
  9. dry with materialdried over MgSO4
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customThe residue was purified by column chromatography (Biotage; 0% to 100% DCM:Hex; 25 g-HP-silica gel column)

Sources & evidence

ORD record
ord-8b37e7ea6dfd47779b26e22d55e45c1a
Source dataset
uspto-grants-2016_08
Patent number
US09402836B2

Reaction notes

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