Succinic anhydride → HCID 18667134, compound

HRID 1455871Notes

Reaction equation

HRID 1455871 reaction equation
[Si:1]([O:8][CH2:9][C@H:10]1[O:14][C@@H:13]([N:15]2[CH:22]=[C:21]([F:23])[C:19](=[O:20])[NH:18][C:16]2=[O:17])[CH2:12][C@@H:11]1[OH:24])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[C:25]1(=[O:31])[O:30][C:28](=[O:29])[CH2:27][CH2:26]1>N1C=CC=CC=1.CN(C)C1C=CN=CC=1.ClCCl>[Si:1]([O:8][CH2:9][C@H:10]1[O:14][C@@H:13]([N:15]2[CH:22]=[C:21]([F:23])[C:19](=[O:20])[NH:18][C:16]2=[O:17])[CH2:12][C@@H:11]1[O:24][C:25](=[O:31])[CH2:26][CH2:27][C:28]([OH:30])=[O:29])([C:4]([CH3:7])([CH3:5])[CH3:6])([CH3:2])[CH3:3]

Participants

6

Reactant 2

HCID 7922Succinic anhydrideHCID 14562110HCID 14562110, compound

Product 1

HCID 18667134HCID 18667134, compoundYield 100.8%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalyst2×HCID 1049PyridineSolventHCID 6344DichloromethaneSolvent

Procedure

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.

Workup

  1. customevaporating the pyridine
  2. customon a rotary evaporator
  3. customTo the thus dried
  4. dissolutionre-dissolved in 20 ml pyridine
  5. customThe flask was sealed with a serum stopper
  6. stirringto stir overnight
  7. customAfter this time, pyridine was removed on the rotary evaporator by co-evaporation with 4×50 ml toluene
  8. customto give a tan foam
  9. extractionextracted with 3×100 ml cold aqueous 10% citric acid
  10. dry with materialThe dichloromethane layer was dried over magnesium sulphate
  11. filtrationfiltered
  12. customthe solvent was removed on a rotary evaporator

Sources & evidence

ORD record
ord-66bd4d3cbb3e405f9ba54aa1aa2a5163
Source dataset
uspto-grants-1998_12
Patent number
US05843917

Reaction notes

Loading…