Sodium Hydroxide → Thymidine, 3'-deoxy-3'-[(triphenylmethyl)amino]-

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Reaction Steps

The 5'-O-anisoyl protecting group was removed by dissolving 2t (30.1 g, 48.7 mmol) in 57:43 1,4-dioxane/MeOH (150 mL), followed by the addition of 2M aq. NaOH (73.1 mL, 146.2 mmol). After stirring for 1.5 h at ambient temperature, the reaction mixture was neutralized with Dowex 50W-X8 cation exchange resin (ca. 150 g of dry pyridinium H+ -form, 1.6 meq/g). Once the pH was neutral (ca. 10 min), the resin was filtered, washed extensively with CH2Cl2 and MeOH, and the crude product was concentrated in vacuo. The residue was redissolved in EtOAc (500 mL) and extracted with saturated. aq. NaHCO3 (2×250 mL), H2O (250 mL), and saturated. aq. NaCl (250 mL). After drying over Na2SO4 and filtration, the solvents were removed in vacuo, and the resulting foam was redissolved in 95:5 CH2Cl2 /MeOH (300 mL). This solution was added slowly to a rapidly stirring mixture of 1:1 Et2O/hexane (1250 mL) to precipitate the pure 3'-(Trityl)amino-3'-deoxythymidine, 3t, in 90% yield (21.2 g, 43.8 mmol). Conversion to phosphoramidite monomers and/or succinylated nucleoside is described in Examples 5-7 below.

Provenance & Evidence