Dimethyl Sulfoxide → (2s)-Glycidyl indol-4-yl ether

HRID 1760201Notes

Reaction equation

HRID 1760201 reaction equation
C([O-])([O-])=O.[K+].[K+].CS(C)=O.[OH:11][C:12]1[CH:20]=[CH:19][CH:18]=[C:17]2[C:13]=1[CH:14]=[CH:15][NH:16]2.S(C1C=CC([N+]([O-])=O)=CC=1)(O[CH2:25][C@H:26]1[O:28][CH2:27]1)(=O)=O>CC(C)=O.O>[O:28]1[CH2:27][C@H:26]1[CH2:25][O:11][C:12]1[CH:20]=[CH:19][CH:18]=[C:17]2[C:13]=1[CH:14]=[CH:15][NH:16]2

Participants

7

Reactant 4

HCID 679Dimethyl SulfoxideHCID 11430Potassium CarbonateHCID 754211H-indol-4-olHCID 10868995(S)-(+)-Glycidyl-4-nitrobenzoate

Product 1

HCID 10943254(2s)-Glycidyl indol-4-yl etherYield 84.7%

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 962WaterSolvent

Procedure

Powdered K2CO3 (40 grams, 289 mmol, 300 mesh) was added to dimethyl sulfoxide (DMSO) (200 mL) containing H2O (4 mL) under N2 at room temperature and the mixture was stirred for 30 minutes. 4-Hydroxyindole (25.2 grams, 189 mmol) was added to the mixture (slight exotherm to 27° C.) and the mixture was stirred for 10 minutes. (S)-Glycidyl nosylate (50.0 grams, 193 mmol, 98.5% ee) was added (slight endotherm). The slurry was stirred for 30 minutes at 20-25° C. and for 23 hours at 25-27° C. until the reaction was complete. The mixture was diluted with acetone (400 mL) and filtered. The cake was washed with acetone (400 mL) and the combined filtrates were concentrated to a volume of ca. 250 mL under vacuum while maintaining the temperature below 35° C. This concentrate was added dropwise, over ca. 2 hours, to deionized H2O (650 mL) held at a temperature of 15-20° C. with an ice/water bath. The product slurry was stirred for 1 hour at this temperature and for 30 minutes at 5-10° C. The solid was isolated by filtration and washed with cold deionized H2O (150 mL). The solid was dried under vacuum at 35° C. to yield 30.3 grams of product.

Workup

  1. stirringthe mixture was stirred for 10 minutes
  2. stirringThe slurry was stirred for 30 minutes at 20-25° C. and for 23 hours at 25-27° C. until the reaction
  3. filtrationfiltered
  4. washThe cake was washed with acetone (400 mL)
  5. concentrationthe combined filtrates were concentrated to a volume of ca. 250 mL under vacuum
  6. temperaturewhile maintaining the temperature below 35° C
  7. additionThis concentrate was added dropwise, over ca. 2 hours, to deionized H2O (650 mL)
  8. customheld at a temperature of 15-20° C. with an ice/water bath
  9. stirringThe product slurry was stirred for 1 hour at this temperature and for 30 minutes at 5-10° C
  10. customThe solid was isolated by filtration
  11. washwashed with cold deionized H2O (150 mL)
  12. customThe solid was dried under vacuum at 35° C.

Sources & evidence

ORD record
ord-b1701f3541f444ccb18fb318075bfbdc
Source dataset
uspto-grants-2005_01
Patent number
US06841563B1

Reaction notes

Loading…