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

HRID 2369454Notes

Reaction equation

HRID 2369454 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]([CH2:24][CH:25]([CH3:27])[CH3:26])[S:12]([C:15]1[CH:20]=[CH:19][C:18]([N+:21]([O-])=O)=[CH:17][CH:16]=1)(=[O:14])=[O:13])(C)(C)C.N(CCO)(CCO)CCO>CO.[C].[Pd]>[NH2:21][C:18]1[CH:19]=[CH:20][C:15]([S:12]([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)[CH2:24][CH:25]([CH3:27])[CH3:26])(=[O:14])=[O:13])=[CH:16][CH:17]=1

Participants

5

Reactant 2

HCID 7618TriethanolamineHCID 10279676tert-Butyl ((1S,2R)-1-benzyl-2-hydroxy-3-(isobutyl((4-nitrophenyl)sulfonyl)amino)propyl)carbamate

Product 1

HCID 9888792N-((2R,3S)-3-Amino-2-hydroxy-4-phenylbutyl)-N-(2-methylpropyl)-4-aminobenzenesulfonamideYield 95%

Reagents, catalysts & solvents 2

HCID 178418390HCID 178418390, compoundCatalystHCID 887MethanolSolvent

Procedure

The compound of formula 3a (100 g), 10% palladium carbon (10 g) and triethanolamine (2 g) were suspended in methanol and then hydrogenated at 40-45° C. for 2 h. After completion of the reaction (TLC monitoring), filtered the reaction mass to remove palladium carbon. cp. HCl (62 mL) was added to the filtrate, heated to reflux and maintained for 2 h. The reaction mass was cooled to ambient temperature, pH of the reaction mass was adjusted to 6.0-7.0 with 20% sodium hydroxide solution. Methanol was distilled off under vacuum at below 50° C. The resultant residue was dissolved in a mixture of isopropyl alcohol (300 mL) and purified water (600 mL) and pH was further adjusted to 9.0-10.0 with 20% sodium hydroxide solution at ambient temperature. The reaction mass was maintained for 10 h, cooled to 0-5° C., filtered and washed with purified water. The wet cake was suspended in isopropyl alcohol (350 mL), heated to reflux, and maintained for 30 min. The reaction mass was cooled to 2-4° C., maintained for 1 h., filtered and washed with isopropyl alcohol. The wet product was air dried to obtain the compound of formula 4 in 71.3 g (yield-95%) with HPLC purity of 99.76%.

Workup

  1. customAfter completion of the reaction (TLC monitoring)
  2. filtrationfiltered the reaction mass
  3. customto remove palladium carbon
  4. additionHCl (62 mL) was added to the filtrate
  5. temperatureheated
  6. temperatureto reflux
  7. temperaturemaintained for 2 h
  8. distillationMethanol was distilled off under vacuum at below 50° C
  9. dissolutionThe resultant residue was dissolved in a mixture of isopropyl alcohol (300 mL)
  10. custompurified water (600 mL)
  11. custompH was further adjusted to 9.0-10.0 with 20% sodium hydroxide solution at ambient temperature
  12. temperatureThe reaction mass was maintained for 10 h
  13. temperaturecooled to 0-5° C.
  14. filtrationfiltered
  15. washwashed with purified water
  16. temperatureheated
  17. temperatureto reflux
  18. temperaturemaintained for 30 min
  19. temperatureThe reaction mass was cooled to 2-4° C.
  20. temperaturemaintained for 1 h.
  21. filtrationfiltered
  22. washwashed with isopropyl alcohol
  23. customdried

Sources & evidence

ORD record
ord-660de0adfaae45faa1df4f8ec41ea5b0
Source dataset
uspto-grants-2014_04
Patent number
US08703980B2

Reaction notes

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