Phosphoric Acid → Sacubitril Impurity 72

HRID 1525637노트

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HRID 1525637 반응식
[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

참가 물질

6

반응물 4

HCID 1004Phosphoric AcidHCID 3939Lithium HydroxideHCID 8028TetrahydrofuranHCID 66584503HCID 66584503, 화합물

생성물 1

HCID 56847899Sacubitril Impurity 72

시약·촉매·용매 1

HCID 8857Ethyl Acetate용매

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-adcebcaf1c5346f398faecf3c78a7822
출처 데이터셋
uspto-grants-2015_07
특허 번호
US09085529B2

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