Sulfuric acid magnesium salt (1:1) → Fingolimod Impurity 4

HRID 617581Notes

Reaction equation

HRID 617581 reaction equation
[H-].[Al+3].[Li+].[H-].[H-].[H-].[C:7]([NH:10][CH:11]([CH2:16][CH2:17][C:18]1[CH:23]=[CH:22][C:21]([CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH3:31])=[CH:20][CH:19]=1)[C:12](OC)=[O:13])(=[O:9])[CH3:8].S([O-])([O-])(=O)=O.[Mg+2]>O1CCCC1>[C:7]([NH:10][CH:11]([CH2:16][CH2:17][C:18]1[CH:23]=[CH:22][C:21]([CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH3:31])=[CH:20][CH:19]=1)[CH2:12][OH:13])(=[O:9])[CH3:8]

Participants

5

Reactant 3

HCID 24083Sulfuric acid magnesium salt (1:1)HCID 21226445Aluminium lithium hydrideHCID 22618836Methyl 2-acetamido-4-(4-octylphenyl)butyrate

Product 1

HCID 22618882Fingolimod Impurity 4Yield 65.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a suspension of lithium aluminum hydride (1.2 g) in tetrahydrofuran (100 ml), a solution of methyl 2-acetamido-4-(4-octylphenyl)butyrate (11 g) in tetrahydrofuran (200 ml) was added and the suspension was stirred at room temperature for 30 minutes. An aqueous tetrahydrofuran (70%, 10 ml) was added to the solution and the mixture was left standing overnight. Magnesium sulfate was added to the mixture, the precipitate was filtered off and the solvent was distilled away under reduced pressure. The residue was dissolved in ethyl acetate, the solution was washed with a dilute hydrochloric acid, an aqueous sodium hydrogencarbonate solution and a saturated brine in order and dried over sodium sulfate. The solvent was distilled away under reduced pressure to give the subject compound (6.6 g).

Workup

  1. waitthe mixture was left
  2. waitstanding overnight
  3. filtrationthe precipitate was filtered off
  4. distillationthe solvent was distilled away under reduced pressure
  5. dissolutionThe residue was dissolved in ethyl acetate
  6. washthe solution was washed with a dilute hydrochloric acid
  7. dry with materialan aqueous sodium hydrogencarbonate solution and a saturated brine in order and dried over sodium sulfate
  8. distillationThe solvent was distilled away under reduced pressure

Sources & evidence

ORD record
ord-5d2086f1ffe04edfb9c125689c48f348
Source dataset
uspto-grants-1999_09
Patent number
US05948820

Reaction notes

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