Hydrochloric Acid → (2S,4R)-4-amino-5-biphenyl-4-yl-2-hydroxymethyl-2-methyl-pentanoic acid (S)-2-methoxycarbonylamino-3-methyl-butyryloxymethyl ester

HRID 448643Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 448643
Cl[CH2:2][O:3][C:4](=[O:14])[C@@H:5]([NH:9][C:10]([O:12][CH3:13])=[O:11])[CH:6]([CH3:8])[CH3:7].[C:15]1([C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)[CH:20]=[CH:19][C:18]([CH2:21][C@@H:22]([NH:31]C(OC(C)(C)C)=O)[CH2:23][C@:24]([CH2:29][OH:30])([CH3:28])[C:25]([OH:27])=[O:26])=[CH:17][CH:16]=1.CCN(CC)CC.Cl.O1CCOCC1>CC(C)=O.CC#N>[CH3:13][O:12][C:10]([NH:9][C@@H:5]([CH:6]([CH3:8])[CH3:7])[C:4]([O:3][CH2:2][O:27][C:25](=[O:26])[C@@:24]([CH2:29][OH:30])([CH3:28])[CH2:23][C@H:22]([NH2:31])[CH2:21][C:18]1[CH:19]=[CH:20][C:15]([C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)=[CH:16][CH:17]=1)=[O:14])=[O:11]

Komponenten

8

Edukt 5

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 312751,4-DioxaneHCID 68181022(2S,4R)-5-Biphenyl-4-yl-4-t-butoxycarbonylamino-2-hydroxymethyl-2-methyl-pentanoic acidHCID 86669865(S)-chloromethyl 2-((methoxycarbonyl)amino)-3-methylbutanoate

Produkt 1

HCID 86669864(2S,4R)-4-amino-5-biphenyl-4-yl-2-hydroxymethyl-2-methyl-pentanoic acid (S)-2-methoxycarbonylamino-3-methyl-butyryloxymethyl ester

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 180AcetoneLösungsmittelHCID 6342AcetonitrileLösungsmittel

Versuchsvorschrift

(S)-2-Methoxycarbonylamino-3-methyl-butyric acid chloromethyl ester (140 mg, 630 μmol) was added to a mixture of (2S,4R)-5-biphenyl-4-yl-4-t-butoxycarbonylamino-2-hydroxymethyl-2-methyl-pentanoic acid (0.2 g, 484 μmol) and Et3N (71 μL, 508 μmol) in acetone (10 mL). The mixture was refluxed for 24 hours and the reaction monitored for completion. When the reaction was complete, the product was purified (Interchim reverse phase chromatography column) the solvent was removed under vacuum. MeCN (2 mL) and 4 M HCl in 1,4-dioxane (2 mL, 8 mmol) was added and the resulting mixture was stirred for 30 minutes. The solvent was evaporated under vacuum and the product was azeotroped with toluene (1×) to yield (2S,4R)-4-amino-5-biphenyl-4-yl-2-hydroxymethyl-2-methyl-pentanoic acid (S)-2-methoxycarbonylamino-3-methyl-butyryloxymethyl ester.

Aufarbeitung

  1. temperatureThe mixture was refluxed for 24 hours
  2. customthe product was purified (Interchim reverse phase chromatography column) the solvent
  3. customwas removed under vacuum
  4. customThe solvent was evaporated under vacuum
  5. customthe product was azeotroped with toluene (1×)

Quellen und Nachweise

ORD-Eintrag
ord-4402dcbaa7464f34ab33386ab0d658e0
Quelldatensatz
uspto-grants-2013_07
Patentnummer
US08481044B2

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