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

HRID 1489455Notes

Reaction equation

HRID 1489455 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.[CH3:18][C:19]([Si:22](Cl)([C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)([CH3:21])[CH3:20]>CN(C1C=CN=CC=1)C.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:19]([CH3:21])([CH3:20])[CH3:18])([C:29]1[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=1)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1

Participants

5

Reactant 2

HCID 5789ThymidineHCID 94078tert-Butyldiphenylchlorosilane

Product 1

HCID 118128465'-O-tert-Butyldiphenylsilyl-thymidineYield 88%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 1049PyridineSolvent

Procedure

A stirring solution of thymidine (50.0 g, 207 mmol) and DMAP (10 mg, 8.2×10-2 mmol) in 400 mL of pyridine was treated with TBDPSCl (43.4 g, 248 mmol) at 25° C. for 16 h. The solvent was removed under reduced pressure and the residue was diluted with 1 L of AcOEt. The mixture was washed with 5% aqueous HCl (2×100 mL) and H2O (100 mL). The organic layer was dried (MgSO4) and concentrated under reduced pressure. The product was purified by silica gel chromatography (CH2Cl2 /MeOH 20:1) to give 87.3 g (88%) of 2 as a white solid. An analytical sample was crystallized from diethylether. mp 164°-166° C. (170°-171° C. per Matulic-Adamic, J. Chem. Soc., Chem. Comm. 1985, 21, 1535) Rf (CH2Cl2 /MeOH 10:1) 0.31. 1H-NMR (CDCl3): 1.08 (s, 9H, C-Me3), 1.61 (s, 3H, 5-Me), 2.18 (ddd, 1H, J=13.8, 8.5, 6.0 Hz, 2'Hβ), 2.19 (br s, 1H, D2O exchangeable, 3'-OH), 2.44 (ddd, 1H, J=13.8, 5.6, 2.1 Hz, 2'-Hα), 3.25 (br s, 1H, 5'-OH, D2O exchangeable), 3.85 (dd, 1H, J=11.5, 2.5 Hz, 5'-CHH), 3.98 (dd, 1H J=11.5, 2.3 Hz, 5'-CHH), 4.06 (dd, 1H, J=2.5, 2.3 Hz, 4'H), 4.55 (dd, 1H J=6.0, 5.6 Hz, 3'-H), 6.43 (dd, 1H, J=8.5, 5.6 Hz, 1'-H), 7.26-7.51 (m, 6H, aromatic-H), 7.64-7.68 (m, 5H, 6-H and aromatic-H), 9.57 (s, 1H, NH, D2O exchangeable).

Workup

  1. customThe solvent was removed under reduced pressure
  2. additionthe residue was diluted with 1 L of AcOEt
  3. washThe mixture was washed with 5% aqueous HCl (2×100 mL) and H2O (100 mL)
  4. dry with materialThe organic layer was dried (MgSO4)
  5. concentrationconcentrated under reduced pressure
  6. customThe product was purified by silica gel chromatography (CH2Cl2 /MeOH 20:1)

Sources & evidence

ORD record
ord-5732ed0e06714bd4b42028ebc5a03480
Source dataset
uspto-grants-1997_10
Patent number
US05677437

Reaction notes

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