Triethanolamine → N-((2R,3S)-3-Amino-2-hydroxy-4-phenylbutyl)-N-(2-methylpropyl)-4-aminobenzenesulfonamide

HRID 1505573Notes

Reaction equation

HRID 1505573 reaction equation
C(OC(=O)[NH:7][C@@H:8]([CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[C@H:9]([OH:28])[CH2:10][N:11]([S:16]([C:19]1[CH:24]=[CH:23][C:22]([N+:25]([O-])=O)=[CH:21][CH:20]=1)(=[O:18])=[O:17])[CH2:12][CH:13]([CH3:15])[CH3:14])(C)(C)C.N(CCO)(CCO)CCO.[H][H].[OH-].[Na+]>C(O)(C)C.[C].[Pd]>[NH2:25][C:22]1[CH:23]=[CH:24][C:19]([S:16]([N:11]([CH2:10][C@@H:9]([OH:28])[C@@H:8]([NH2:7])[CH2:29][C:30]2[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=2)[CH2:12][CH:13]([CH3:15])[CH3:14])(=[O:18])=[O:17])=[CH:20][CH:21]=1

Participants

7

Reactant 4

HCID 7618TriethanolamineHCID 14798Sodium HydroxideHCID 10279676tert-Butyl ((1S,2R)-1-benzyl-2-hydroxy-3-(isobutyl((4-nitrophenyl)sulfonyl)amino)propyl)carbamateHCID 178418361HCID 178418361, compound

Product 1

HCID 9888792N-((2R,3S)-3-Amino-2-hydroxy-4-phenylbutyl)-N-(2-methylpropyl)-4-aminobenzenesulfonamideYield 79.9%

Reagents, catalysts & solvents 2

HCID 178418390HCID 178418390, compoundCatalystHCID 3776IsopropanolSolvent

Conditions

Temperature
42.5 °C

Procedure

(1S,2R)-{1-benzyl-2-hydroxy-3-[isobutyl-(4-nitro-benzenesulfonyl)-amino]-propyl}-carbamic acid tert-butyl ester (3, 100 g), 10% palladium carbon (10 gm) and triethanolamine (2 gm) were suspended in isopropyl alcohol. The reaction was heated to 40-45° C. and maintained under 4-6 kg/cm2 of hydrogen pressure for 3 hours. After completion of reaction, the mass was filtered and hydrochloric acid (70 mL) was added to the filtered mass. The solution was heated to reflux and maintained for 2-3 hours. After completion of reaction the mass was cooled to 25-35° C., the reaction mass pH was adjusted to 6.0-7.0 with 20% sodium hydroxide solution and distilled out isopropyl alcohol under vacuum at below 55° C. Ethanol (200 mL) and water (400 mL) was added to the distillate, the mass pH was adjusted to 9.0-10.0 with 20% sodium hydroxide solution at 25-35° C. and maintained the stirring for 2 hours at 25-35° C. The mass was cooled to 0-5° C., filtered and wash with water. The wet product was taken into ethanol (350 mL), maintained the stirring for 30 minutes at reflux temperature. The mass was cooled to 2-4° C., stirred for 2 hours, filtered and washed with ethanol (50 mL). The wet product was dried under normal drying to get title compound 1 (Yield 60 g).

Workup

  1. customAfter completion of reaction
  2. filtrationthe mass was filtered
  3. additionhydrochloric acid (70 mL) was added to the filtered mass
  4. temperatureThe solution was heated
  5. temperatureto reflux
  6. temperaturemaintained for 2-3 hours
  7. customAfter completion of reaction the mass
  8. temperaturewas cooled to 25-35° C.
  9. distillationdistilled out isopropyl alcohol under vacuum at below 55° C
  10. additionEthanol (200 mL) and water (400 mL) was added to the distillate
  11. customwas adjusted to 9.0-10.0 with 20% sodium hydroxide solution at 25-35° C.
  12. temperaturemaintained the stirring for 2 hours at 25-35° C
  13. temperatureThe mass was cooled to 0-5° C.
  14. filtrationfiltered
  15. washwash with water
  16. temperaturemaintained the stirring for 30 minutes
  17. temperatureat reflux temperature
  18. temperatureThe mass was cooled to 2-4° C.
  19. filtrationfiltered
  20. washwashed with ethanol (50 mL)
  21. customThe wet product was dried
  22. customunder normal drying

Sources & evidence

ORD record
ord-e9fa9ad86a79482fae187aaff9b28bbb
Source dataset
uspto-grants-2015_12
Patent number
US09216990B2

Reaction notes

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