Hydrochloric Acid → Treprostinil

HRID 885776Notes

Reaction equation

HRID 885776 reaction equation
[CH3:1][CH2:2][CH2:3][CH2:4][CH2:5][C@H:6]([OH:28])[CH2:7][CH2:8][C@@H:9]1[C@H:13]2[CH2:14][C:15]3[CH:21]=[CH:20][CH:19]=[C:18]([O:22][CH2:23][C:24]([OH:26])=[O:25])[C:16]=3[CH2:17][C@H:12]2[CH2:11][C@H:10]1[OH:27].C(NCCO)CO.O.Cl>C(OCC)(=O)C>[CH3:1][CH2:2][CH2:3][CH2:4][CH2:5][C@H:6]([OH:28])[CH2:7][CH2:8][C@H:9]1[C@H:10]([OH:27])[CH2:11][C@H:12]2[C@@H:13]1[CH2:14][C:15]1[C:16]([CH2:17]2)=[C:18]([O:22][CH2:23][C:24]([OH:26])=[O:25])[CH:19]=[CH:20][CH:21]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 962WaterHCID 11179459Treprostinil diolamine

Product 1

HCID 6918140TreprostinilYield 92%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

A 250-mL, round-bottom flask equipped with magnetic stirrer was charged with treprostinil diethanolamine salt (4 g) and water (40 mL). The mixture was stirred to obtain a clear solution. To the clear solution, ethyl acetate (100 mL) was added. While stirring, 3M HCl (3.2 mL) was added slowly until pH 1 was attained. The mixture was stirred for 10 minutes and organic layer was separated. The aqueous layer was extracted with ethyl acetate (2×100 mL). The combined organic layers was washed with water (2×100 mL), brine (1×50 mL) and dried over anhydrous Na2SO4. The ethyl acetate solution of treprostinil was filtered and the filtrate was concentrated under vacuum at 50° C. to give off-white solid. The crude treprostinil was recrystallized from 50% ethanol in water (70 mL). The pure treprostinil was collected in a Buchner funnel by filtration and cake was washed with cold 20% ethanolic solution in water. The cake of treprostinil was air-dried overnight and further dried in a vacuum oven at 50° C. under high vacuum to afford 2.9 g of treprostinil (Yield 91.4%, purity (HPLC, AUC, 99.8%).

Workup

  1. customA 250-mL, round-bottom flask equipped with magnetic stirrer
  2. customto obtain a clear solution
  3. stirringWhile stirring
  4. stirringThe mixture was stirred for 10 minutes
  5. customorganic layer was separated
  6. extractionThe aqueous layer was extracted with ethyl acetate (2×100 mL)
  7. washThe combined organic layers was washed with water (2×100 mL), brine (1×50 mL)
  8. dry with materialdried over anhydrous Na2SO4
  9. filtrationThe ethyl acetate solution of treprostinil was filtered
  10. concentrationthe filtrate was concentrated under vacuum at 50° C.
  11. customto give off-white solid
  12. customThe crude treprostinil was recrystallized from 50% ethanol in water (70 mL)
  13. filtrationThe pure treprostinil was collected in a Buchner funnel by filtration and cake
  14. washwas washed with cold 20% ethanolic solution in water
  15. dry with materialThe cake of treprostinil was air-dried overnight
  16. customfurther dried in a vacuum oven at 50° C. under high vacuum

Sources & evidence

ORD record
ord-23bacff39c934eeb87007988688164e8
Source dataset
uspto-grants-2012_08
Patent number
US08242305B2

Reaction notes

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