4-Toluenesulfonyl chloride → Nod-IN-1

HRID 1080558Notes

Reaction equation

HRID 1080558 reaction equation
[H-].[Na+].[CH2:3]([O:5][C:6]([C:8]1[NH:9][C:10]2[C:15]([CH:16]=1)=[CH:14][CH:13]=[CH:12][CH:11]=2)=[O:7])[CH3:4].[C:17]1([CH3:27])[CH:22]=[CH:21][C:20]([S:23](Cl)(=[O:25])=[O:24])=[CH:19][CH:18]=1>C1COCC1>[CH2:3]([O:5][C:6]([C:8]1[N:9]([S:23]([C:20]2[CH:21]=[CH:22][C:17]([CH3:27])=[CH:18][CH:19]=2)(=[O:25])=[O:24])[C:10]2[C:15]([CH:16]=1)=[CH:14][CH:13]=[CH:12][CH:11]=2)=[O:7])[CH3:4]

Participants

5

Reactant 3

HCID 73974-Toluenesulfonyl chlorideHCID 24758Sodium hydrideHCID 73125Ethyl indole-2-carboxylate

Product 1

HCID 14783456Nod-IN-1

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
30 °C

Procedure

To a stirred suspension of sodium hydride (3.7 g, 120 mmol, 80% in paraffin oil) in dry THF (75 mL), a solution of indol-2-carboxylic acid ethyl ester (18.9 g, 100 mmol) in dry THF (75 mL) was added in 1 hour with stirring while the inner temperature was maintained under 30° C. The reaction mixture was stirred for 30 minutes and then a solution of p-toluenesulphonyl chloride (22.9 g, 120 mmol) in dry THF (75 mL) was added dropwise to the stirring reactant. After 2 hours stirring at room temperature and 1 hour at 45° C. the solvent was evaporated in vacuo and the residue partitioned between water and ethyl ether. The organic phase was dried over MgSO4 and the solvent evaporated to leave a solid which was recrystallized from diisopropyl ether (26.8 g, 78%), mp 92°-950° C.

Workup

  1. stirringThe reaction mixture was stirred for 30 minutes
  2. stirringAfter 2 hours stirring at room temperature and 1 hour at 45° C. the solvent
  3. customwas evaporated in vacuo
  4. customthe residue partitioned between water and ethyl ether
  5. dry with materialThe organic phase was dried over MgSO4
  6. customthe solvent evaporated
  7. customto leave a solid which
  8. customwas recrystallized from diisopropyl ether (26.8 g, 78%), mp 92°-950° C.

Sources & evidence

ORD record
ord-21afb9df96974abf9264556ac959c129
Source dataset
uspto-grants-1996_12
Patent number
US05580896

Reaction notes

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