Ethanol → Sacubitril Impurity 3

HRID 1477455Notes

Reaction equation

HRID 1477455 reaction equation
[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

Participants

7

Reactant 3

HCID 702EthanolHCID 58160391HCID 58160391, compoundHCID 178418361HCID 178418361, compound

Product 2

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

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 8471TriethylamineSolvent

Procedure

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.

Workup

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

Sources & evidence

ORD record
ord-bef14dd85220406a8902ace87224fd43
Source dataset
uspto-grants-2016_08
Patent number
US09403766B2

Reaction notes

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