反应 #1543053

反应方程式

succinic anhydride

5'-O-(tert-Butyldimethylsilyl)-2'-deoxy-5-fluorouridine

→

tan foam

收率 100.8%

5'-O-(tert-Butyldimethylsilyl)-3'-O-(3-Carboxypropionyl)-2'-deoxy-5-fluorouridine

收率 100.8%

溶剂

dichloromethane

pyridine

反应条件

后处理

1. 1
   其他evaporating the pyridine
2. 2
   其他on a rotary evaporator
3. 3
   其他To the thus dried
4. 4
   workup.DISSOLUTIONre-dissolved in 20 ml pyridine
5. 5
   其他The flask was sealed with a serum stopper
6. 6
   workup.STIRRINGto stir overnight
7. 7
   其他After this time, pyridine was removed on the rotary evaporator by co-evaporation with 4×50 ml toluene
8. 8
   其他to give a tan foam
9. 9
   萃取extracted with 3×100 ml cold aqueous 10% citric acid
10. 10
    干燥The dichloromethane layer was dried over magnesium sulphate
11. 11
    过滤filtered
12. 12
    其他the solvent was removed on a rotary evaporator

实验过程

4.0 g (11.0 mmol) of 5'-O-(tert-Butyldimethylsilyl)-2'-deoxy-5-fluorouridine was dried by twice dissolving the nucleoside in 25 ml of anhydrous pyridine in a round bottom flask and evaporating the pyridine on a rotary evaporator. To the thus dried protected nucleoside re-dissolved in 20 ml pyridine was added 0.54 g (4.4 mmol) of 4-dimethylaminopyridine all at once and 0.84 g (8.4 mmol) succinic anhydride (Aldrich Chemical Company, Milwaukee, Wis. 53233) in three portions over 90 min. After stirring for 2.5 hrs, another equal portion of 4-dimethylaminopyridine was added. The flask was sealed with a serum stopper and the mixture was allowed to stir overnight. After this time, pyridine was removed on the rotary evaporator by co-evaporation with 4×50 ml toluene to give a tan foam. The foam was dissolved in 100 ml dichloromethane and extracted with 3×100 ml cold aqueous 10% citric acid, followed by 100 ml water. The dichloromethane layer was dried over magnesium sulphate, filtered, and the solvent was removed on a rotary evaporator to give 3.9 g of a tan foam. This foam was dissolved in a minimal amount of dichloromethane and applied to a column (4.5×30 cm) packed with silica gel (350 g, 230-400 mesh) in dichloromethane. Under medium air pressure (9-12 psi) the column was first eluted with 1 L of chloroform followed by elution with 1 L of 1% methanol in chloroform. The percentage of methanol was increased 1% for each successive litre. The product was eluted into fractions between 2% and 10% methanol in chloroform. Product fractions were pooled and the solvent was removed on the rotary evaporator to give 2.0 g (4.3 mmol) of a white solid: m.p. 133.4°-135.3° C.

来源