1-Methylimidazole → 5'-Deoxy-5-fluorocytidine
Reaction equation
C[N:2]1C=CN=C1.P(Cl)(Cl)(Cl)=O.C([O:20][C@@H:21]1[C@H:25]([O:26]C(=O)C2C=CC=CC=2)[C@@H:24]([CH3:35])[O:23][C@H:22]1[N:36]1[CH:43]=[C:42]([F:44])[C:40](=O)[NH:39][C:37]1=[O:38])(=O)C1C=CC=CC=1.[OH-].[NH4+]>C(#N)C>[F:44][C:42]1[C:40]([NH2:2])=[N:39][C:37](=[O:38])[N:36]([CH:43]=1)[C@@H:22]1[O:23][C@H:24]([CH3:35])[C@@H:25]([OH:26])[C@H:21]1[OH:20]Participants
Procedure
To a mixture of N-methylimidazole (0.8 ml) and phosphoryl chloride (0.28 ml) in acetonitrile (20 ml) was added 2',3'-di-O-benzoyl-5'-deoxy-5-fluorouridine (500 mg) obtained above at 0° C. After stirring of the reaction mixture for 1.5 hours at room temperature 28% ammonium hydroxide (2.5 ml) was added to the mixture at 0° C., and the mixture was stirred for 1 hour at room temperature. Acetonitrile and ammonia were removed under reduced pressure. The residue was acidified with 1N-HCl and then extracted with ethyl acetate. The organic layer was washed with water, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was recrystallized from ethyl acetate to give 155 mg of 2',3'-di-O-benxoyl- 5'-deoxy-5-fluorocytidine, mp 192°~194° C.; MS 476 ((M+Na)+).
Workup
- customobtained above at 0° C
- additionwas added to the mixture at 0° C.
- customAcetonitrile and ammonia were removed under reduced pressure
- extractionextracted with ethyl acetate
- washThe organic layer was washed with water
- dry with materialdried over anhydrous sodium sulfate
- concentrationconcentrated under reduced pressure
- customThe residue was recrystallized from ethyl acetate
Sources & evidence
- ORD record
- ord-26fa1d2236fd4819a2298b048de21c8d
- Source dataset
- uspto-grants-1990_10
- Patent number
- US04966891
Reaction notes
Loading…