Potassium Hydroxide → Stavudine

HRID 1735936Notes

Reaction equation

HRID 1735936 reaction equation
[OH-].[K+].[C@@H:3]1([N:10]2[CH:18]=[C:16]([CH3:17])[C:14](=[O:15])[NH:13][C:11]2=[O:12])[O:9][C@@H:6]2[CH2:7][O:8][C@H:5]2[CH2:4]1>C(O)(C)C>[C@@H:3]1([N:10]2[CH:18]=[C:16]([CH3:17])[C:14](=[O:15])[NH:13][C:11]2=[O:12])[O:9][C@H:6]([CH2:7][OH:8])[CH:5]=[CH:4]1

Participants

4

Reactant 2

HCID 14797Potassium HydroxideHCID 140694703',5'-Anhydrothymidine

Product 1

HCID 18283StavudineYield 81.6%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent2×

Conditions

Temperature
50 °C

Procedure

A five liter, three-necked flask was equipped with an overhead stirrer and paddle, a reflux condenser, a temperature probe, and a heating mantle. Isopropanol (1.25 L) and potassium hydroxide (198 g, 3.0 moles) were added to the flask and heated to 50° C. stirring. Then, 3', 5'-anhydrothymidine (168.2 g, 0.75 mole) was added portion-wise. The resulting solution was then heated at 78°-80° C. for 3.5 hours. The solution was cooled to 20°-25° C., diluted with isopropanol (1.75 L), then taken to pH 4-6 with concentrated HCI and cooled to 0° C. The precipitated KCl was filtered off and washed with isopropanol (200 mL). The combined filtrate and wash was divided into three equal portions. Each portion was mixed with N-methylpyrrolidinone (54 mL) and concentrated to a thick oil at 50° C./15-20 mm Hg, then diluted with acetone (120 mL) and warmed at 50° C. for 15 minutes. The mixture was then cooled to 15° C., forming a thick slurry. The solids were collected by filtration to give a total of 65.96 g (81.6%) of the title compound which assays 68.5% (by weight) d4T.

Workup

  1. customA five liter, three-necked flask was equipped with an overhead stirrer
  2. temperatureThe resulting solution was then heated at 78°-80° C. for 3.5 hours
  3. temperatureThe solution was cooled to 20°-25° C.
  4. concentrationwith concentrated HCI
  5. temperaturecooled to 0° C
  6. filtrationThe precipitated KCl was filtered off
  7. washwashed with isopropanol (200 mL)
  8. washThe combined filtrate and wash
  9. additionEach portion was mixed with N-methylpyrrolidinone (54 mL)
  10. concentrationconcentrated to a thick oil at 50° C./15-20 mm Hg
  11. additiondiluted with acetone (120 mL)
  12. temperaturewarmed at 50° C. for 15 minutes
  13. temperatureThe mixture was then cooled to 15° C.
  14. customforming a thick slurry
  15. filtrationThe solids were collected by filtration

Sources & evidence

ORD record
ord-144a013bf60548309d5a70028285622e
Source dataset
uspto-grants-1996_07
Patent number
US05539099

Reaction notes

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