Ethanol → Sacubitril Impurity 3

HRID 1477455Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1477455
[C:1]1([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH:6]=[CH:5][C:4]([CH2:7][C@H:8]2[NH:12][C:11](=[O:13])[CH:10]([CH2:14]I)[CH2:9]2)=[CH:3][CH:2]=1.C(O)C.[H][H]>[Pd].C(N(CC)CC)C>[C:1]1([C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=2)[CH:2]=[CH:3][C:4]([CH2:7][C@H:8]2[NH:12][C:11](=[O:13])[C@H:10]([CH3:14])[CH2:9]2)=[CH:5][CH:6]=1.[C:1]1([C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=2)[CH:2]=[CH:3][C:4]([CH2:7][C@H:8]2[NH:12][C:11](=[O:13])[C@@H:10]([CH3:14])[CH2:9]2)=[CH:5][CH:6]=1

Komponenten

7

Edukt 3

HCID 702EthanolHCID 58160391HCID 58160391, VerbindungHCID 178418361HCID 178418361, Verbindung

Produkt 2

HCID 59318451Sacubitril Impurity 3HCID 667391582-Pyrrolidinone, 5-([1,1'-biphenyl]-4-ylMethyl)-3-Methyl-, (3R,5S)-

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 23938PalladiumKatalysatorHCID 8471TriethylamineLösungsmittel

Versuchsvorschrift

4 mg (3R/S,5S)-5-Biphenyl-4-ylmethyl-3-iodomethyl-pyrrolidin-2-one (12-a, R1=H, R5=I) is added to ethanol (1 ml) at ambient temperature. Triethylamine (5 μl) is then added to the mixture. 0.4 mg Palladium on carbon (10%, 50% water-wet, Degussa E101 NE/W) is then added. Hydrogen gas at ambient pressure is applied to the mixture. The mixture is then stirred overnight at ambient temperature and pressure. The mixture is then filtered and concentrated under reduced pressure to afford (3R,5S)-5-biphenyl-4-ylmethyl-3-methylpyrrolidin-2-one (3-a, R1=H) and (3S,5S)-5-biphenyl-4-ylmethyl-3-methylpyrrolidin-2-one (3-b, R1=H. Ratio of diastereomers 22:88 (3-a, R1=H to 3-b, R1=H) as determined by nmr. Spectroscopic data for 3-a (R1=H) as for Example 6 in WO/2008/083967. Spectroscopic data for 3-b (R1=H) as for Example 47 in WO/2008/083967.

Aufarbeitung

  1. filtrationThe mixture is then filtered
  2. concentrationconcentrated under reduced pressure

Quellen und Nachweise

ORD-Eintrag
ord-bef14dd85220406a8902ace87224fd43
Quelldatensatz
uspto-grants-2016_08
Patentnummer
US09403766B2

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