5'-O-(4,4'-DIMETHOXYTRITYL)-2'-FLUORO-D-URIDINE

An operation of dissolving 2’-Deoxy-2’-fluorouridine (3.00 g, 12.2 mmol) in dry pyridine, followed by concentrationunder reduced pressure was repeated 3 times to perform dehydrative azeotropic distillation. Thereafter, under an argonatmosphere, the reaction mixture was dissolved in dry pyridine (120 ml), 4, 4’-dimethoxytrityl chloride (4.55 g, 13.4 mmol)was added, and the mixture was stirred at room temperature for 3 hr. The completion of the reaction was confirmed, and ethyl acetate (150 ml) and water (60 ml) were added to the reaction mixture to allow layer separation. The organiclayer was washed 3 times with 5percent aqueous sodium hydrogen carbonate solution (20 ml), washed with water (20 ml)and saturated brine (20 ml), and the obtained organic layer was dried over sodium sulfate. The solvent in the filtrate wasevaporated and the obtained residue was purified by silica gel column chromatography (hexane:ethyl acetate = 50:50- 0/100(v/v), containing 1percent triethylamine). The object fractions were collected and concentrated to give the title compound(8.48 g, quant).(1) A solution of 2’-deoxy-2’-fluorouridine (6g, 24.37 mmol) and 4, 4'-(chloro(phenyl) methylene)-bis(methoxybenzene) (9.91 g, 29.2 mmol) in pyridine (48.7 ml) was stirred at rt for 16 hours. The mixture was treated with MeOH (20 mL), concentrated to dryness and was partitioned between water (50 mL) and EtOAc (250 mL). The aqueous phase was back extracted with EtOAc (50 mL) and the combined organic layers were washed with water (50 A solution of 2'-deoxy-2'-fluorouridine (6g, 24.37 mmol) and 4, 4'-(chloro(phenyl) methylene)-bis(methoxybenzene) (9.91 g, 29.2 mmol) in pyridine (48.7 ml) was stirred at rt for 16 hours. The mixture was treated with MeOH (20 mL), concentrated to dryness and was partitioned between water (50 mL) and EtOAc (250 mL). The aqueous phase was back extracted with EtOAc (50 mL) and the combined organic layers were washed with water (50 mL) and dried over Na2S04 The solution was concentrated to give 2'-deoxy-2'- fluoro-5'-(4', 4'-dimethoxytrityl)uridine (14g, quant.) which was used without further purification.A solution of 2'-deoxy-2'-fluorouridine (6g, 24.37 mmol) and 4, 4'-(chloro(phenyl) methylene)-bis(methoxybenzene) (9.91 g, 29.2 mmol) in pyridine (48.7 ml) was stirred at rt for 16 hours. The mixture was treated with MeOH (20 mL), concentrated to dryness and was partitioned between water (50 mL) and EtOAc (250 mL). The aqueous phase was back extracted with EtOAc (50 mL) and the combined organic layers were washed with water (50 mL) and dried over Na2S04. The solution was concentrated to give 2'-deoxy-2'-fluoro-5'-(4', 4'- dimethoxytrityl)uridine (14g, quant.) which was used without further purification.General procedure: To a mixture of diol 1a-23a (1.0 mmol) and dimethoxy triphenylmethonol 1or 2 (1.1 mmol) in dichloromethane (10 mL), 10 mol percent of Cu(NO3)2.H2O(copper(II)nitrate monohydrate is highly oxidizing and irritant) was added and theblue heterogeneous reaction mixture refluxed for 3–24 h. After completion of thestarting material 1a-23a, (monitored by TLC), the reaction mixture was diluted withdichloromethane and washed with water (1 × 10 mL) and brine (1 × 10 mL). Theorganic layer was dried overNa2SO4 and evaporated to get crude product. The crudecompound was purified by column chromatography (30percent ethylacetate in hexane to80percent ethylacetate in hexane) to afford compound 1b-4b 17b-11b & 19b-20b or 5c-10c, 12c-18c & 21c-23c.

Molecular Weight:548.6
XLogP3:3.6
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:8
Rotatable Bond Count:9
Exact Mass:548.19587943
Monoisotopic Mass:548.19587943
Topological Polar Surface Area:107
Heavy Atom Count:40
Complexity:873
Defined Atom Stereocenter Count:4
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes