Hydrochloric Acid → Treprostinil

HRID 1803471Notes

Reaction equation

HRID 1803471 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.C(OCC)(=O)C.Cl>O>[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 8857Ethyl AcetateHCID 11179459Treprostinil diolamine

Product 1

HCID 6918140Treprostinil

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A 3.34-kg sample of treprostinil diethanolamine salt was dissolved in 40 L of sterile water, 60 L of ethyl acetate and 3.2 L of 3 M HCl were added and the mixture stirred. The layers were separated and the aqueous layer was extracted thrice with 20-L portions of ethyl acetate. The four organic layers were combined, the organic solution washed twice with 20-L portions of sterile water, once with 20 L of brine and dried over 2.97 kg of anhydrous sodium sulfate. The mixture was filtered and the filtrate was concentrated to yield treprostinil as a gummy solid. This solid was transferred to glass drying trays and let air-dry for 93 hours. This solid was then dissolved in 23.4 kg of ethanol, warmed to 48° C. and treated with 23.4 kg of warm (40-50° C.) sterile water. The solution was stirred and then stirring was stopped to allow the treprostinil to slowly crystallize. The resulting white solid was collected by filtration in an Aurora filter, washed with 45 L of a cold (6° C.) 20% ethanol in sterile water solution, the filter moved to a Hepa-filtered Finishing Room and the solid dried under house vacuum for 22.3 hours. The solid was transferred to drying trays and further dried in a vacuum oven at 55 deg. C and 0.26 Torr for 22.7 hours to give 2.63 kg (96.3%) of anhydrous treprostinil (Lot #01A07002) as a white solid.

Workup

  1. customThe layers were separated
  2. extractionthe aqueous layer was extracted thrice with 20-L portions of ethyl acetate
  3. washthe organic solution washed twice with 20-L portions of sterile water, once with 20 L of brine
  4. dry with materialdried over 2.97 kg of anhydrous sodium sulfate
  5. filtrationThe mixture was filtered
  6. concentrationthe filtrate was concentrated

Sources & evidence

ORD record
ord-2641c383f50d48efa042fdfe592c8506
Source dataset
uspto-grants-2013_01
Patent number
US08350079B2

Reaction notes

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