Ethanol → Sacubitril Impurity 3

HRID 2041677노트

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HRID 2041677 반응식
[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

참가 물질

7

반응물 3

HCID 702EthanolHCID 58160391HCID 58160391, 화합물HCID 178418361HCID 178418361, 화합물

생성물 2

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

시약·촉매·용매 2

HCID 23938Palladium촉매HCID 8471Triethylamine용매

실험 절차

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.

후처리

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

출처 및 근거

ORD 기록
ord-6d1bda9fa7444a06ab3c569d9ff99b96
출처 데이터셋
uspto-grants-2013_11
특허 번호
US08580974B2

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