Hydrochloric Acid → Fingolimod Hydrochloride

HRID 1505022Notes

Reaction equation

HRID 1505022 reaction equation
[OH:1][CH2:2][C:3]([NH:22]C(=O)C)([CH2:20][OH:21])[CH2:4][CH2:5][C:6]1[CH:11]=[CH:10][C:9]([CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH3:19])=[CH:8][CH:7]=1.[ClH:26]>>[CH3:19][CH2:18][CH2:17][CH2:16][CH2:15][CH2:14][CH2:13][CH2:12][C:9]1[CH:10]=[CH:11][C:6]([CH2:5][CH2:4][C:3]([NH2:22])([CH2:2][OH:1])[CH2:20][OH:21])=[CH:7][CH:8]=1.[ClH:26]

Participants

3

Reactant 2

HCID 313Hydrochloric Acid2×HCID 10521783N-(1-hydroxy-2-(hydroxymethyl)-4-(4-octylphenyl)butan-2-yl)acetamide

Product 1

HCID 107969Fingolimod Hydrochloride

Conditions

Temperature
100 °C

Procedure

N-(1-Hydroxy-2-(hydroxymethyl)-4-(4-octylphenyl)butan-2-yl) acetamide (23.5 g) is charged into a 250 mL single-neck round bottom flask equipped with a condenser and 3N hydrochloric acid (100 mL) is added. The mixture is heated to 100° C. and stirred for 3 hours. The mass is cooled to room temperature and maintained overnight. The mass is extracted with ethyl acetate (3×100 mL) and the ethyl acetate extracts are combined, dried with sodium sulphate, and concentrated under vacuum to produce a gummy solid. Ethanolic hydrochloride solution is added to the solid, stirred for 3 hours at room temperature and the obtained solid is separated by filtration and suction dried. The solid is recrystallized from an isopropyl alcohol solution to give fingolimod hydrochloride. Yield: 5.7 g.

Workup

  1. customequipped with a condenser
  2. temperatureThe mass is cooled to room temperature
  3. temperaturemaintained overnight
  4. extractionThe mass is extracted with ethyl acetate (3×100 mL)
  5. dry with materialdried with sodium sulphate
  6. concentrationconcentrated under vacuum
  7. customto produce a gummy solid
  8. stirringstirred for 3 hours at room temperature
  9. customthe obtained solid is separated by filtration and suction
  10. customdried
  11. customThe solid is recrystallized from an isopropyl alcohol solution

Sources & evidence

ORD record
ord-c52c55e4b0684fd8876722d6181252c6
Source dataset
uspto-grants-2015_12
Patent number
US09216943B2

Reaction notes

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