Thymidine → 5'-O-tert-Butyldiphenylsilyl-thymidine

HRID 2395841Notes

Reaction equation

HRID 2395841 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.[C:18]([Si:22]([C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)([C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)Cl)([CH3:21])([CH3:20])[CH3:19]>CN(C)C1C=CN=CC=1.N1C=CC=CC=1>[Si:22]([O:7][CH2:6][C@H:5]1[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][C@@H:3]1[OH:4])([C:18]([CH3:21])([CH3:20])[CH3:19])([C:30]1[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=1)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1

Participants

5

Reactant 2

HCID 5789ThymidineHCID 94078tert-Butyldiphenylchlorosilane2×

Product 1

HCID 118128465'-O-tert-Butyldiphenylsilyl-thymidineYield 144.7%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 1049PyridineSolvent

Procedure

A mixture of thymidine (400 g, and 1.65 mol), 4-dimethylaminopyridine (0.8 g, 6.5 mmol) and t-butyldiphenylchlorosilane (347.2 g, 1.26 mol) in anhydrous pyridine (3.0 lt) was stirred at room temperature for 48 hr. To the stirred reaction mixture two lots of t-butyldiphenyl chlorosilane (129.4 g, 0.47 mol and 22.7 g, 0.082 mol) were added 12 hr. apart and stirring continued for an additional 48 hr. The reaction mixture was concentrated under vacuum and the residue redissolved in methanol (2.5 lt). The product was precipitated by pouring the reaction mixture into a cold stirred ice-water (5.0 lt) suspension. The aqueous suspension was stirred at room temperature for 3 hr. to quench traces of unreacted chlorosilane. The granular white precipitate was filtered and washed with distilled water (5×1 lt) and air dried to furnish 876 g of 5'-O-t-butyldiphenylsilyl thymidine (slightly contaminated with bissilyated product, about 5%). The impurity was removed by suspending finely powdered 5'-O-t-butyldiphenylsilyl thymidine in ether (600 ml) and pouring into stirred hexanes (1.5 lt).

Workup

  1. additionwere added 12 hr
  2. stirringapart and stirring
  3. waitcontinued for an additional 48 hr
  4. concentrationThe reaction mixture was concentrated under vacuum
  5. dissolutionthe residue redissolved in methanol (2.5 lt)
  6. customThe product was precipitated
  7. additionby pouring the reaction mixture into
  8. stirringa cold stirred ice-water (5.0 lt) suspension
  9. stirringThe aqueous suspension was stirred at room temperature for 3 hr
  10. customto quench traces of unreacted chlorosilane
  11. filtrationThe granular white precipitate was filtered
  12. washwashed with distilled water (5×1 lt) and air
  13. customdried

Sources & evidence

ORD record
ord-6a0b67bb9a6a4b159dc3e8da0f70a78a
Source dataset
uspto-grants-1996_02
Patent number
US05489677

Reaction notes

Loading…