Dimethyl Sulfoxide → 2-((Tert-butoxycarbonyl)amino)-3-(4-carbamoyl-2,6-dimethylphenyl)propanoic acid

HRID 2371015Notes

Reaction equation

HRID 2371015 reaction equation
C[O:2][C:3](=[O:25])[CH:4]([NH:17][C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:5][C:6]1[C:11]([CH3:12])=[CH:10][C:9]([C:13](=[O:15])[NH2:14])=[CH:8][C:7]=1[CH3:16].CS(C)=O.OO.C(=O)([O-])[O-].[K+].[K+]>O>[C:21]([O:20][C:18]([NH:17][CH:4]([CH2:5][C:6]1[C:11]([CH3:12])=[CH:10][C:9]([C:13](=[O:15])[NH2:14])=[CH:8][C:7]=1[CH3:16])[C:3]([OH:25])=[O:2])=[O:19])([CH3:24])([CH3:23])[CH3:22]

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 784Hydrogen PeroxideHCID 11430Potassium CarbonateHCID 235707192-tert-Butoxycarbonylamino-3-(4-carbamoyl-2,6-dimethyl-phenyl)-propionic acid methyl ester

Product 1

HCID 221476672-((Tert-butoxycarbonyl)amino)-3-(4-carbamoyl-2,6-dimethylphenyl)propanoic acid

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
43.5 °C

Procedure

2-tert-Butoxycarbonylamino-3-(4-carbamoyl-2,6-dimethyl-phenyl)-propionic acid methyl ester (250 g, 0.713 mol), DMSO (750 mL) and 30% H2O2 (250 mL), were added to a 5 L three-necked round bottom flask equipped with addition funnel, mechanical stirrer, heating mantel, reflux condenser, thermocouple and nitrogen inlet. Potassium carbonate (158 g, 1.14 mol, 1.6 eq) was dissolved in water (750 mL) and added dropwise over 30 minutes. During the addition, a temperature increase was observed (from 23° C. to 34° C.). The resulting mixture was warmed up to about 42-45° C. and the progress of the reaction monitored by HPLC. After 3 hours, to the warm mixture was added activated carbon (ECOSORB-941) (37.5 g, 15% by weight). The resulting slurry was refluxed for 1 hour, and then filtered hot through CELITE®. The CELITE® pad was rinsed with H2O (1.5 L). The resulting mixture was cooled to about 10° C. and quenched with 2.0N HCl (pH 2, 1.22 L), to yield a mixture comprising a white solid precipitated. The mixture was aged under agitation for a period of about 4 hours in an ice bath and then filtered and dried for 48 hours in a vacuum oven to yield the title compound as a white crystalline solid.

Workup

  1. customequipped with addition funnel, mechanical stirrer
  2. temperatureheating mantel
  3. temperaturereflux condenser
  4. additionadded dropwise over 30 minutes
  5. additionDuring the addition
  6. temperaturea temperature increase
  7. custom(from 23° C. to 34° C.)
  8. additionto the warm mixture was added activated carbon (ECOSORB-941) (37.5 g, 15% by weight)
  9. temperatureThe resulting slurry was refluxed for 1 hour
  10. filtrationfiltered hot through CELITE®
  11. washThe CELITE® pad was rinsed with H2O (1.5 L)
  12. temperatureThe resulting mixture was cooled to about 10° C.
  13. customquenched with 2.0N HCl (pH 2, 1.22 L)
  14. customto yield a mixture
  15. customprecipitated
  16. waitThe mixture was aged under agitation for a period of about 4 hours in an ice bath
  17. filtrationfiltered
  18. customdried for 48 hours in a vacuum oven

Sources & evidence

ORD record
ord-a1c99cc1589548d7a5d890c8802d1fb7
Source dataset
uspto-grants-2014_04
Patent number
US08710256B2

Reaction notes

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