Hydrochloric Acid → 3',5'-DI-O-Mesylthymidine

HRID 1735933Notes

Reaction equation

HRID 1735933 reaction equation
[C@@H:1]1([N:9]2[CH:17]=[C:15]([CH3:16])[C:13](=[O:14])[NH:12][C:10]2=[O:11])[O:8][C@H:5]([CH2:6][OH:7])[C@@H:3]([OH:4])[CH2:2]1.CN1CCOCC1.[CH3:25][S:26](Cl)(=[O:28])=[O:27].Cl>O.CC(C)=O>[CH3:25][S:26]([O:4][C@@H:3]1[C@@H:5]([CH2:6][O:7][S:26]([CH3:25])(=[O:28])=[O:27])[O:8][C@@H:1]([N:9]2[CH:17]=[C:15]([CH3:16])[C:13](=[O:14])[NH:12][C:10]2=[O:11])[CH2:2]1)(=[O:28])=[O:27]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 5789ThymidineHCID 79724-MethylmorpholineHCID 31297Methanesulfonyl chlorideHCID 178435160HCID 178435160, compound

Product 1

HCID 105729323',5'-DI-O-MesylthymidineYield 94.5%

Reagents, catalysts & solvents 2

HCID 180AcetoneSolvent2×HCID 962WaterSolvent

Procedure

A five liter, three-necked, round bottom flask was equipped with an overhead stirrer and paddle, a 500 mL dropping funnel, a Claisen adapter with thermocouple probe and a reflux condenser. Thymidine (363.3 g, 1.5 moles) and N-methylmorpholine (508.3 g, 5.02 moles) were added to the flask with acetone (2.00 L). The mixture was stirred while adding methanesulfonyl chloride (498.3 g, 4.35 moles) slowly over about one hour, with cooling to maintain 30°-35° C. during the addition. An additional 1.50 L of acetone was added to the mixture to maintain adequate stirring. After the addition was complete, the mixture was stirred for 1 hour at 30°-35° C. The reaction was then transferred in portions to water (9.66 L) being stirred in a 20 L polyethylene tank. The pH of the aqueous slurry was adjusted with 12N HCl to pH 2.5 and stirred at ambient temperature for an additional two hours. The slurry was filtered and the solid was washed with water (2.9 L) and isopropanol (1.45 L). The solid was air dried overnight to give 564.6 g (94.5%) of the title compound which assays 97.1% (by weight) purity.

Workup

  1. customA five liter, three-necked, round bottom flask was equipped with an overhead stirrer
  2. temperaturewith cooling
  3. temperatureto maintain 30°-35° C. during the addition
  4. temperatureto maintain adequate stirring
  5. additionAfter the addition
  6. stirringthe mixture was stirred for 1 hour at 30°-35° C
  7. stirringstirred at ambient temperature for an additional two hours
  8. filtrationThe slurry was filtered
  9. washthe solid was washed with water (2.9 L) and isopropanol (1.45 L)
  10. customdried overnight

Sources & evidence

ORD record
ord-79d930e8b49444b59c3d11ec90ff1efb
Source dataset
uspto-grants-1996_07
Patent number
US05539099

Reaction notes

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