Phosphoric Acid → Sacubitril Impurity 72

HRID 1525637ノート

反応式

HRID 1525637 の反応式
[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

参加物

6

反応物 4

HCID 1004Phosphoric AcidHCID 3939Lithium HydroxideHCID 8028TetrahydrofuranHCID 66584503HCID 66584503、化合物

生成物 1

HCID 56847899Sacubitril Impurity 72

試薬・触媒・溶媒 1

HCID 8857Ethyl Acetate溶媒

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-adcebcaf1c5346f398faecf3c78a7822
出典データセット
uspto-grants-2015_07
特許番号
US09085529B2

反応ノート

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