Ethanol → Sacubitril Impurity 3

HRID 1477455ノート

反応式

HRID 1477455 の反応式
[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

参加物

7

反応物 3

HCID 702EthanolHCID 58160391HCID 58160391、化合物HCID 178418361HCID 178418361、化合物

生成物 2

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

試薬・触媒・溶媒 2

HCID 23938Palladium触媒HCID 8471Triethylamine溶媒

実験手順

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.

後処理

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

出典と根拠

ORDレコード
ord-bef14dd85220406a8902ace87224fd43
出典データセット
uspto-grants-2016_08
特許番号
US09403766B2

反応ノート

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