Phosphoric Acid → Sacubitril Impurity 72

HRID 1525637Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1525637
[C:1]([O:5][C:6]([N:8]1[C@H:12]([CH2:13][C:14]2[CH:19]=[CH:18][C:17]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)=[CH:16][CH:15]=2)[CH:11]=[C:10]([CH3:26])[C:9]1=[O:27])=[O:7])([CH3:4])([CH3:3])[CH3:2].[O:28]1CCCC1.[OH-].[Li+].P(=O)(O)(O)O>C(OCC)(=O)C>[C:17]1([C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=2)[CH:18]=[CH:19][C:14]([CH2:13][C@@H:12]([NH:8][C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])/[CH:11]=[C:10](/[CH3:26])\[C:9]([OH:28])=[O:27])=[CH:15][CH:16]=1

Komponenten

6

Edukt 4

HCID 1004Phosphoric AcidHCID 3939Lithium HydroxideHCID 8028TetrahydrofuranHCID 66584503HCID 66584503, Verbindung

Produkt 1

HCID 56847899Sacubitril Impurity 72

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

2.7 g (R)-5-Biphenyl-4-ylmethyl-3-methyl-2-oxo-2,5-dihydro-pyrrole-1-carboxylic acid tert-butyl ester (4-a, R1=Boc) is added to tetrahydrofuran (20 ml). Aqueous lithium hydroxide solution (10 ml, 3 M) is added and the mixture is stirred for 20 h at ambient temperature. The mixture is acidified by addition of phosphoric acid and subsequently diluted by addition of ethyl acetate. The phases are separated and the organic phase is washed with water and then concentrated under reduced pressure. Isopropyl acetate is added to the residue and the mixture is filtered to afford (Z)—(R)-5-Biphenyl-4-yl-4-tert-butoxycarbonylamino-2-methylpent-2-enoic acid (5a, R1=Boc, R2=H, R3=CO2H). 1H NMR (DMSO): 1.28 (9H), 1.85 (3H), 2.78 (2H), 5.07 (1H), 5.92 (1H), 6.96 (1H), 7.30 (2H), 7.35 (1H), 7.46 (2H), 7.56 (2H), 7.63 (2H), 12.65 (1H).

Aufarbeitung

  1. customThe phases are separated
  2. washthe organic phase is washed with water
  3. concentrationconcentrated under reduced pressure
  4. additionIsopropyl acetate is added to the residue
  5. filtrationthe mixture is filtered

Quellen und Nachweise

ORD-Eintrag
ord-adcebcaf1c5346f398faecf3c78a7822
Quelldatensatz
uspto-grants-2015_07
Patentnummer
US09085529B2

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