Hydrochloric Acid → Fingolimod Hydrochloride

HRID 1028876Notes

Reaction equation

HRID 1028876 reaction equation
[OH:1][CH2:2][C:3]([N+:23]([O-])=O)([CH2:21][OH:22])[CH2:4][CH:5]([C:7]1[CH:12]=[CH:11][C:10]([CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH3:20])=[CH:9][CH:8]=1)O.[H][H].[ClH:28]>CO.[C].[Pd]>[CH3:20][CH2:19][CH2:18][CH2:17][CH2:16][CH2:15][CH2:14][CH2:13][C:10]1[CH:11]=[CH:12][C:7]([CH2:5][CH2:4][C:3]([NH2:23])([CH2:2][OH:1])[CH2:21][OH:22])=[CH:8][CH:9]=1.[ClH:28]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 668364203-(Hydroxymethyl)-3-nitro-1-(4-octylphenyl)butane-1,4-diolHCID 178418361HCID 178418361, compound

Product 1

HCID 107969Fingolimod Hydrochloride

Reagents, catalysts & solvents 2

HCID 178418390HCID 178418390, compoundCatalystHCID 887MethanolSolvent

Procedure

To 14.1 g (0.04 mol) of 3-(hydroxymethyl)-3-nitro-1-(p-octylphenyl)butane-1,4-diol in 250 ml of methyl alcohol, 30 ml of concentrated hydrochloric acid was added, followed by the catalyst—10% palladium-carbon. The mixture was stirred at 20 kg/cm2 hydrogen pressure for two days at room temperature. The mixture was then filtered, methyl alcohol was distilled off, the residue was dissolved in water, adjusted to pH 8 with saturated sodium bicarbonate, and extracted with ethyl acetate (100 ml×3). The ethyl acetate extracts were dried over magnesium sulfate, filtered, evaporated. The residue was dissolved in ethanol (50 ml) and a 1N hydrochloric acid (50 ml) was added thereto. The mixture was stirred for 1 h, the solvent was distilled off and the resultant solid were recrystallized from ethanol to give Fingolimod hydrochloride.

Workup

  1. filtrationThe mixture was then filtered
  2. distillationmethyl alcohol was distilled off
  3. dissolutionthe residue was dissolved in water
  4. extractionextracted with ethyl acetate (100 ml×3)
  5. dry with materialThe ethyl acetate extracts were dried over magnesium sulfate
  6. filtrationfiltered
  7. customevaporated
  8. dissolutionThe residue was dissolved in ethanol (50 ml)
  9. additiona 1N hydrochloric acid (50 ml) was added
  10. distillationthe solvent was distilled off
  11. customthe resultant solid were recrystallized from ethanol

Sources & evidence

ORD record
ord-e1b8cd1e942047a18aaa2973a8af516b
Source dataset
uspto-grants-2014_05
Patent number
US08735627B2

Reaction notes

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