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

HRID 2393716Notes

Reaction equation

HRID 2393716 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 ethanol (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 it) and air dried to furnish 876 g of 5'-O-t-butyldiphenylsilyl thymidine (slightly contaminated with bissilyated product, about 5%).

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 ethanol (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 it) and air
  13. customdried

Sources & evidence

ORD record
ord-6668fa229fb64d8589f0b07d53c1e9f3
Source dataset
uspto-grants-1998_09
Patent number
US05808023

Reaction notes

Loading…