4-Toluenesulfonyl chloride → HCID 90421554, compound

HRID 1054888Notes

Reaction equation

HRID 1054888 reaction equation
[CH3:1][O:2][C:3]([C:5]1[C:13]2[C:8](=[CH:9][C:10]([Cl:15])=[C:11]([Br:14])[CH:12]=2)[NH:7][CH:6]=1)=[O:4].[H-].[Na+].[CH3:18][C:19]1[CH:24]=[CH:23][C:22]([S:25](Cl)(=[O:27])=[O:26])=[CH:21][CH:20]=1>CN(C)C=O>[CH3:1][O:2][C:3]([C:5]1[C:13]2[C:8](=[CH:9][C:10]([Cl:15])=[C:11]([Br:14])[CH:12]=2)[N:7]([S:25]([C:22]2[CH:23]=[CH:24][C:19]([CH3:18])=[CH:20][CH:21]=2)(=[O:27])=[O:26])[CH:6]=1)=[O:4]

Participants

5

Reactant 3

HCID 73974-Toluenesulfonyl chlorideHCID 24758Sodium hydrideHCID 86698569methyl 5-bromo-6-chloro-1H-indole-3-carboxylate

Product 1

HCID 90421554HCID 90421554, compoundYield 89%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 5-bromo-6-chloro-1H-indole-3-carboxylic acid methyl ester (80.0 g, 277 mmol) in N,N-dimethylformamide (600 mL) at 0° C. was added sodium hydride (60% dispersion in oil, 16.6 g, 416 mmol) portion-wise over 20 minutes. The reaction was stirred at 0° C. for 60 minutes followed by the addition of 4-methylbenzenesulphonyl chloride (63.4 g, 333 mmol), which was added portion-wise to the stirring solution. The reaction was allowed to stir for 2 hours at 0° C. and the ice bath was removed and the reaction was allowed to warm to room temperature and stirred overnight. The reaction was poured into water (1200 mL) and stirred for 12 hours. The suspension was filtered and the filter cake was washed with a further portion of water (700 mL) then heptane (2×300 mL), 160 g of crude material was recovered. The material was placed in a 3 L round bottom flask and placed on rotorary evaporated with a 40° C. bath under vacuum overnight to remove residual water. This afforded 116 g of pink solid which was suspended in acetone (600 mL) and heated to reflux for 1 hour, then removed from the heat, cooled to room temperature, and stirred for a further hour. The suspension was filtered and the filter cake was washed with acetone (˜500 mL) until the filtrate was colorless. The filter cake was dried to afford desired product (108.7 g, 89% yield). 1H NMR (CDCl3, 400 MHz) 5=8.39 (s, 1 H) 8.24 (s, 1 H) 8.11 (s, 1 H) 7.82 (d, J=8.59 Hz, 2 H) 7.32 (d, J=8.20 Hz, 2 H) 3.93 (s, 3 H) 2.40 (s, 3 H); MS (ES+) 441.9 (M+H)+.

Workup

  1. additionwas added portion-wise to the stirring solution
  2. stirringto stir for 2 hours at 0° C.
  3. customthe ice bath was removed
  4. temperatureto warm to room temperature
  5. stirringstirred overnight
  6. additionThe reaction was poured into water (1200 mL)
  7. stirringstirred for 12 hours
  8. filtrationThe suspension was filtered
  9. washthe filter cake was washed with a further portion of water (700 mL)
  10. customheptane (2×300 mL), 160 g of crude material was recovered
  11. customThe material was placed in a 3 L round bottom flask
  12. customon rotorary evaporated with a 40° C. bath under vacuum overnight
  13. customto remove residual water
  14. temperatureheated
  15. temperatureto reflux for 1 hour
  16. customremoved from the heat
  17. temperaturecooled to room temperature
  18. stirringstirred for a further hour
  19. filtrationThe suspension was filtered
  20. washthe filter cake was washed with acetone (˜500 mL) until the filtrate
  21. customThe filter cake was dried

Sources & evidence

ORD record
ord-1d85c7bc9b3e47799478d51a719343a0
Source dataset
uspto-grants-2016_07
Patent number
US09394285B2

Reaction notes

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