Potassium Hydroxide → 5-[2-(Tert-butyldimethylsiloxy)ethyl]-4-chloro-7-[2-c-methyl-3,5-bis-o-(2,4-dichlorophenylmethyl)-beta-d-ribofuranosyl]-7h-pyrrolo[2,3-d]pyrimidine

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Reaction Steps

Compound 2.3 (2.5 g, 8.00 mmol) was suspended in CH3CN (50 mL), and powdered 85% KOH, (1.3 g, 19.73 mmol) followed by TDA -1 (tris[2-(2-methoxyethoxy)ethyl]amine) (0.2 mL, 0.62 mmol) were added. After stirring at room temperature for 10 min, a freshly prepared solution of bromo sugar 2.4 (prepared from commercially available 3,5-bis-O-(2,4-dichlorophenylmethyl)-2-C-methyl-1-O-methyl-α-D-ribofuranose; (i) Helv. Chim. Acta, 1995, 78, 486; (ii) WO 02/057287, 2002) (10.1 mmol) in anhydrous acetonitrile (50 mL) was added via cannula, and the reaction stirred for 24 hr at room temperature then cooled in an ice/water bath and treated with CH2Cl2 (100 mL) and water (80 mL). The aqueous material was extracted three times with CH2Cl2, the combined organic layers were dried over Na2SO4, filtered and evaporated The crude product was purified on a silica gel column using 20% ethyl acetate/hexanes as eluent to give the desired nucleoside 2.5 (1.03 g, 13%). Further elution with 25% EtOAc/hexanes as eluent gave a mixture of the desired nucleoside 2.5 and starting base 2.3 (350 mg).

Provenance & Evidence