Fingolimod Hydrochloride → 2-Amino-2-(fluoromethyl)-4-(4-octylphenyl)butan-1-ol

HRID 526296Notes

Reaction equation

HRID 526296 reaction equation
[CH3:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][C:9]1[CH:14]=[CH:13][C:12]([CH2:15][CH2:16][C:17]([NH2:22])([CH2:20]O)[CH2:18][OH:19])=[CH:11][CH:10]=1.Cl.C(N(S(F)(F)[F:30])CC)C.C(=O)(O)[O-].[Na+]>ClCCl>[NH2:22][C:17]([CH2:20][F:30])([CH2:16][CH2:15][C:12]1[CH:13]=[CH:14][C:9]([CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2][CH3:1])=[CH:10][CH:11]=1)[CH2:18][OH:19]

Participants

5

Reactant 3

HCID 107969Fingolimod HydrochlorideHCID 123472(Diethylamino)sulfur trifluorideHCID 516892Sodium Bicarbonate

Product 1

HCID 226188712-Amino-2-(fluoromethyl)-4-(4-octylphenyl)butan-1-ol

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-78 °C

Procedure

FTY 720 (310 mg, 1.00 mmol) was suspended in dry dichloromethane (10 mL) and cooled down to −78° C. Diethylaminosulfur trifluoride (DAST, 0.13 mL, 1.00 mmol, 1.0 eq.) was slowly added to this suspension and the mixture was allowed to warm up to r.t. overnight. The reaction was neutralized with saturated sodium bicarbonate solution (30 mL) at −10° C. The phases were separated and the aqueous phase was extracted with dichloromethane (3×20 mL). The combined organic layers were dried over MgSO4 and the solvent was removed under reduced pressure. The residue was purified by column chromatography (silica gel, 20×3 cm, dichloromethane/methanol, 4:1) and subsequently by gradient HPLC (RP-HPLC Nucleodur 100-10 C18ec column (250×16 mm), acetonitrile/water (0.1% TFA)) with a Knauer HPLC system. The obtained TFA salt was dissolved in methanol (1 mL) and 1 M sodium hydroxide solution (3 mL) and the mixture was extracted with dichloromethane (5×5 mL). The organic phases were dried over Na2SO4 and concentrated. The product was dried in high vacuum and obtained as highly viscous oil. Yield: 5 mg (2%).

Workup

  1. temperatureto warm up to r.t. overnight
  2. customThe phases were separated
  3. extractionthe aqueous phase was extracted with dichloromethane (3×20 mL)
  4. dry with materialThe combined organic layers were dried over MgSO4
  5. customthe solvent was removed under reduced pressure
  6. customThe residue was purified by column chromatography (silica gel, 20×3 cm, dichloromethane/methanol, 4:1) and subsequently by gradient HPLC (RP-HPLC Nucleodur 100-10 C18ec column (250×16 mm), acetonitrile/water (0.1% TFA)) with a Knauer HPLC system
  7. dissolutionThe obtained TFA salt was dissolved in methanol (1 mL)
  8. extraction1 M sodium hydroxide solution (3 mL) and the mixture was extracted with dichloromethane (5×5 mL)
  9. dry with materialThe organic phases were dried over Na2SO4
  10. concentrationconcentrated
  11. customThe product was dried in high vacuum
  12. customobtained as highly viscous oil

Sources & evidence

ORD record
ord-2858131d6a854b8d9317c4205cfe1140
Source dataset
uspto-grants-2016_05
Patent number
US09345791B2

Reaction notes

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