TCI Practical Example: Protection of a Diol Moiety Using TIPDSCl₂

We are proud to present the selective cyclic silyl protection of hydroxy groups at 3'- and 5'-positions of uridine by using TIPDSCl₂.

Used Chemicals

• Uridine [U0020]
• 1,3-Dichloro-1,1,3,3-tetraisopropyldisiloxane (= TIPDSCl₂) [D1608]
• Pyridine

Procedure

Uridine (1.0 g, 4.10 mmol) was added to pyridine (13.7 mL) at room temperature and stirred, then TIPDSCl₂ (1.42 g, 4.50 mmol) was added. The reaction mixture was stirred for 7 hours. After ethyl acetate (10 mL) was added to the reaction solution, the organic layer was washed with 0.05 mol/L HCl (10 mL), ion exchanged water (10 mL), and brine (10 mL). The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (dichloromethane:methanol = 10:1) to afford 1 (1.38 g, 69% yield) as a white solid.

Experimenter's Comments

The reaction solution was monitored by UPLC.

Analytical Data

Compound 1

¹H NMR (400 MHz, CDCl₃); δ 8.45 (s, 1H), 7.66 (d, J = 8.1 Hz, 1H), 5.73 (s, 1H), 5.68 (d, J = 7.9 Hz, 1H), 4.39 (m, 1H), 4.21 (m, 2H), 4.09 (m, 1H), 4.02 (m, 1H), 2.98 (s, 1H), 1.10 (m, 28H).

Lead Reference

• Preparation of Zwitterionic Ribonucleoside Phosphoramidites for Solid-Phase siRNA Synthesis
• • R. Smicius, J. Engels, J. Org. Chem. 2008, 73, 4994.