Hydrochloric Acid → 3',5'-Anhydrothymidine

HRID 1735935Notes

Reaction equation

HRID 1735935 reaction equation
CS(O[C@@H:6]1[C@@H:10]([CH2:11][O:12]S(C)(=O)=O)[O:9][C@@H:8]([N:17]2[CH:25]=[C:23]([CH3:24])[C:21](=[O:22])[NH:20][C:18]2=[O:19])[CH2:7]1)(=O)=O.[OH-].[Na+].Cl>O>[C@@H:8]1([N:17]2[CH:25]=[C:23]([CH3:24])[C:21](=[O:22])[NH:20][C:18]2=[O:19])[O:9][C@@H:10]2[CH2:11][O:12][C@H:6]2[CH2:7]1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium Hydroxide2×HCID 105729323',5'-DI-O-Mesylthymidine2×

Product 1

HCID 140694703',5'-AnhydrothymidineYield 75.2%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
50 °C

Procedure

A two liter, four-necked flask was equipped with an overhead stirrer and paddle, a pH probe connected to an automatic titrator, and a thermocouple probe connected to a temperature controller and a heating mantle. Water (350 mL) was added to the flask and about a 20-25% portion of 3',5'-di-O-methanesulfonylthymidine (500 g total, 1.255 moles) was added with stirring. The pH was adjusted to 10.5 with 30% aq. sodium hydroxide and the temperature was raised to 50° C. While maintaining the temperature at 50°-55° C. and the pH at 10.5-11.0, the remaining 3',5'-di-O-methanesulfonylthymidine was added slowly as material dissolved, maintaining a stirrable slurry. A total of 502 g (3.765 moles) of 30% aq. NaOH is added. The reaction mixture is then heated at 70° C. for one hour, then cooled to 10°-15° C. The pH was adjusted to 9.7-9.8 with 12N HCl using cooling to maintain the temperature at 10°-15° C. while crystallization occurred. Finally, the slurry was adjusted to pH 6.0-6.5 with 12N HCI and cooled to 0°-5° C. and filtered. The collected solids were washed with cold (0°-5° C.) water (200 mL) and air dried to give 211.6 g (75.2%) of the title compound, which assays 99.8% (by weight) purity.

Workup

  1. customA two liter, four-necked flask was equipped with an overhead stirrer
  2. additionwas added
  3. temperatureWhile maintaining the temperature at 50°-55° C.
  4. dissolutiondissolved
  5. temperaturemaintaining a stirrable slurry
  6. temperatureThe reaction mixture is then heated at 70° C. for one hour
  7. temperaturecooled to 10°-15° C
  8. temperaturecooling
  9. temperatureto maintain the temperature at 10°-15° C.
  10. customwhile crystallization
  11. temperaturecooled to 0°-5° C.
  12. filtrationfiltered
  13. washThe collected solids were washed with cold (0°-5° C.) water (200 mL) and air
  14. customdried

Sources & evidence

ORD record
ord-650d24c35a4f4471a9b96d1b0f2c99c1
Source dataset
uspto-grants-1996_07
Patent number
US05539099

Reaction notes

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