Sodium Hydroxide → Aliskiren

HRID 744818Notes

Reaction equation

HRID 744818 reaction equation
[OH-].[Na+].Cl.[C:4]([C:7]([CH3:42])([CH3:41])[CH2:8][NH:9][C:10](=[O:40])[C@H:11]([CH:37]([CH3:39])[CH3:38])[CH2:12][C@H:13]([OH:36])[C@@H:14]([NH2:35])[CH2:15][C@@H:16]([CH:32]([CH3:34])[CH3:33])[CH2:17][C:18]1[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[C:20]([O:26][CH2:27][CH2:28][CH2:29][O:30][CH3:31])[CH:19]=1)(=[O:6])[NH2:5]>O>[C:4]([C:7]([CH3:42])([CH3:41])[CH2:8][NH:9][C:10](=[O:40])[C@H:11]([CH:37]([CH3:38])[CH3:39])[CH2:12][C@H:13]([OH:36])[C@@H:14]([NH2:35])[CH2:15][C@@H:16]([CH:32]([CH3:34])[CH3:33])[CH2:17][C:18]1[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[C:20]([O:26][CH2:27][CH2:28][CH2:29][O:30][CH3:31])[CH:19]=1)(=[O:6])[NH2:5]

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 23625795Aliskiren hydrochloride

Product 1

HCID 5493444Aliskiren

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

20 g of ice and 12 ml of 2N NaOH are added in succession to a stirred solution of 2.35 g of 5(S)-amino-4(S)-hydroxy-2(S),7(S)-diisopropyl-8-[4-methoxy-3-(3-methoxypropyloxy)-phenyl]-octanoic acid N-(2-carbamoyl-2,2-dimethyl-ethyl)-amide hydrochloride (Example 137) in 20 ml of water, and the mixture is then extracted with 3×50 ml of tert-butyl methyl ether. The combined organic phases are dried with magnesium sulfate and concentrated by evaporation. 0.232 g of fumaric acid is added to the evaporation residue in 25 ml of methanol. The mixture is stirred until a clear solution has formed and is then concentrated by evaporation. The residue is crystallised from 100 ml of acetonitrile/ethanol=95:5. The crystals are filtered off with suction and dried at 60° C. The title compound is obtained in the form of a white powder having a melting point of 95°-104° C.

Workup

  1. extractionthe mixture is then extracted with 3×50 ml of tert-butyl methyl ether
  2. dry with materialThe combined organic phases are dried with magnesium sulfate
  3. concentrationconcentrated by evaporation
  4. addition0.232 g of fumaric acid is added to the evaporation residue in 25 ml of methanol
  5. customhas formed
  6. concentrationis then concentrated by evaporation
  7. customThe residue is crystallised from 100 ml of acetonitrile/ethanol=95:5
  8. filtrationThe crystals are filtered off with suction
  9. customdried at 60° C

Sources & evidence

ORD record
ord-f8122b2b6f7b4abc85d3c3551fba5ab9
Source dataset
uspto-grants-1996_09
Patent number
US05559111

Reaction notes

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