Sodium t-butoxide → 1,1-Dimethylethyl 6-bromo-1-methyl-1H-indole-3-carboxylate

HRID 1689814Notes

Reaction equation

HRID 1689814 reaction equation
C[O:2][C:3]([C:5]1[C:13]2[C:8](=[CH:9][C:10]([Br:14])=[CH:11][CH:12]=2)[N:7]([CH3:15])[CH:6]=1)=O.[CH3:16][C:17]([CH3:20])([O-:19])[CH3:18].[Na+]>C1(C)C=CC=CC=1>[Br:14][C:10]1[CH:9]=[C:8]2[C:13]([C:5]([C:3]([O:19][C:17]([CH3:20])([CH3:18])[CH3:16])=[O:2])=[CH:6][N:7]2[CH3:15])=[CH:12][CH:11]=1

Participants

4

Reactant 2

HCID 23676156Sodium t-butoxide2×HCID 57443279Methyl 6-bromo-1-methyl-1H-indole-3-carboxylate

Product 1

HCID 593693331,1-Dimethylethyl 6-bromo-1-methyl-1H-indole-3-carboxylateYield 66.1%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Conditions

Temperature
106.5 °C

Procedure

Dissolve 6-bromo-1-methyl-1H-indole-3-carboxylic acid methyl ester (17.16 Kg, 63.98 mol) in toluene (134.5 Kg) under nitrogen atmosphere. Stir at least 15 minutes. Add magnesium sulfate to dry and charcoal to de-colorize the solution and stir at least 30 minutes. Filter the mixture. Dissolve sodium tert-butoxide (21.5 Kg, 223.70 mol) in toluene (43.7 kg) under a nitrogen atmosphere. Add the starting material solution mixture to the sodium tert-butoxide solution and heat the reaction mixture slowly over approximately 2-3 hours to a temperature of 105-108° C. and maintain temperature for 30-60 minutes. Follow by TLC until no starting material is observed. Cool the reaction to room temperature and quench the mixture into water (177.2 Kg) cooled to 0-10° C. Stir the reaction mixture for at least 30 minutes and separate the aqueous layer and emulsion. Wash the organic mixture with brine (2×47.7 Kg) maintaining the emulsion with the aqueous brine wash. Extract the combined aqueous layer with toluene (2×29.9 Kg). Filter organic layer and any emulsion through diatomaceous earth. Wash the filter cake with toluene (6.1 Kg). Wash the combined organic layers with brine (2×47.7 Kg). Add magnesium sulfate (7 Kg) and charcoal (850 g) and stir for 30 minutes. Filter the mixture and concentrate the filtrate at 50-55° C. to the lowest stirrable volume. Discontinue heating and add heptane (47.3 Kg) to the mixture. Cool the suspension to 0-5° C. for at least 2 hours and collect the solids by filtration. Rinse the solids with heptane cooled to 0-5° C. Dry solids at 30-35° C. for 12-72 hours under vacuum to give 13.110 Kg (66%) of the title compound.

Workup

  1. dry with materialAdd magnesium sulfate to dry
  2. stirringstir at least 30 minutes
  3. filtrationFilter the mixture
  4. temperaturemaintain temperature for 30-60 minutes
  5. temperatureCool
  6. customthe reaction to room temperature
  7. customquench the mixture into water (177.2 Kg)
  8. temperaturecooled to 0-10° C
  9. stirringStir the reaction mixture for at least 30 minutes
  10. customseparate the aqueous layer and emulsion
  11. washWash the organic mixture with brine (2×47.7 Kg)
  12. temperaturemaintaining the emulsion with the aqueous brine
  13. washwash
  14. extractionExtract the combined aqueous layer with toluene (2×29.9 Kg)
  15. washWash the filter cake with toluene (6.1 Kg)
  16. washWash the combined organic layers with brine (2×47.7 Kg)
  17. stirringAdd magnesium sulfate (7 Kg) and charcoal (850 g) and stir for 30 minutes
  18. filtrationFilter the mixture
  19. concentrationconcentrate the filtrate at 50-55° C. to the lowest stirrable volume
  20. temperatureDiscontinue heating
  21. additionadd heptane (47.3 Kg) to the mixture
  22. temperatureCool the suspension to 0-5° C. for at least 2 hours
  23. customcollect the solids
  24. filtrationby filtration
  25. washRinse the solids with heptane
  26. temperaturecooled to 0-5° C
  27. customDry solids at 30-35° C. for 12-72 hours under vacuum

Sources & evidence

ORD record
ord-59f4ba4b6ea24d7780a84a4e15a41f06
Source dataset
uspto-grants-2012_04
Patent number
US08153624B2

Reaction notes

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