Thymidine → 5'-O-(4,4'-Dimethoxytrityl)thymidine

HRID 2181379Notes

Reaction equation

HRID 2181379 reaction equation
[C@@H]1(N2C=C(C)C(=O)NC2=O)O[C@H](CO)[C@@H](O)C1.COC1C(OC)=C(C=CC=1)C(Cl)(C1C=CC=CC=1)C1C=CC=CC=1.COC1C=CC(C([O:63][C@@H:64]2[C@@H:68]([CH2:69][O:70][C:71]([C:88]3[CH:93]=[CH:92][CH:91]=[CH:90][CH:89]=3)([C:80]3[CH:85]=[CH:84][C:83]([O:86][CH3:87])=[CH:82][CH:81]=3)[C:72]3[CH:77]=[CH:76][C:75]([O:78][CH3:79])=[CH:74][CH:73]=3)[O:67][C@@H:66]([N:94]3[CH:102]=[C:100]([CH3:101])[C:98](=[O:99])[NH:97][C:95]3=[O:96])[CH2:65]2)(C2C=CC=CC=2)C2C=CC(OC)=CC=2)=CC=1>N1C=CC=CC=1>[CH3:79][O:78][C:75]1[CH:76]=[CH:77][C:72]([C:71]([O:70][CH2:69][C@H:68]2[O:67][C@@H:66]([N:94]3[CH:102]=[C:100]([CH3:101])[C:98](=[O:99])[NH:97][C:95]3=[O:96])[CH2:65][C@@H:64]2[OH:63])([C:88]2[CH:89]=[CH:90][CH:91]=[CH:92][CH:93]=2)[C:80]2[CH:85]=[CH:84][C:83]([O:86][CH3:87])=[CH:82][CH:81]=2)=[CH:73][CH:74]=1

Participants

5

Reactant 3

HCID 5789ThymidineHCID 20771213HCID 20771213, compoundHCID 66624882Dimethoxytrityl chloride

Product 1

HCID 1624195'-O-(4,4'-Dimethoxytrityl)thymidine

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

In a 250-ml three-necked flask, thymidine and dimethoxytrityl chloride in anhydrous pyridine are introduced in succession under inert gas and stirred for 2 hours at room temperature. The TLC control test of the reaction (V(MeOH):V(CH2Cl2)=1:19) shows the 5′-O-protected compound (Rf=0.26) to be the main product. It also contains one faint spot each for the starting material (Rf=0.00) and the doubly protected byproduct, 3′,5′-bis-O-(4,4′-dimethoxytrityl)thymidine (Rf=0.71). The reaction solution is then decanted slowly into 1.5 l of vigorously stirred ice water. After 30 minutes of stirring, the yellow suspension is suction-filtered, and the residual moisture is removed from the solid in the rotary evaporator by azeotropic distillation two times with ethanol. Alternatively, the raw product is recrystallized from a benzene-acetone mixture or is purified by means of column chromatography (silica gel 60; Ø=6 cm; h=45 cm; V(MeOH):V(CH2Cl2)=1:19+0.1% of triethylamine; absorbed on about 20 g of silica gel 60). After drying in high vacuum, it yields the product, 5′-O-(4,4′-dimethoxytrityl)thymidine.

Workup

  1. customThe reaction solution is then decanted slowly into 1.5 l of vigorously stirred ice water
  2. stirringAfter 30 minutes of stirring
  3. filtrationthe yellow suspension is suction-filtered
  4. customthe residual moisture is removed from the solid in the rotary evaporator by azeotropic distillation two times with ethanol
  5. customAlternatively, the raw product is recrystallized from a benzene-acetone mixture
  6. customis purified by means of column chromatography (silica gel 60; Ø=6 cm; h=45 cm; V(MeOH):V(CH2Cl2)=1:19+0.1% of triethylamine; absorbed on about 20 g of silica gel 60)
  7. customAfter drying in high vacuum, it

Sources & evidence

ORD record
ord-bc628920293b4c18b40aeb6f197298fd
Source dataset
uspto-grants-2005_05
Patent number
US06891033B2

Reaction notes

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