反应详情

5'-Deoxy-2',3'-di-O-acetyl-5-fluorocytidine (1.5 g) and dry pyridine (0.74 ml) were dissolved in dry dichloromethane (15 ml). To the mixture, toluene solution of neopentyl chloroformate (3 eq.) was added dropwise at 0° C., and stirred at room temperature for 1 hour. After the solvent was removed under reduced pressure, the residue was partitioned between ether and saturated aqueous solution of sodium carbonate. The organic layer was successively washed with water and brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure to give crude 2',3'-di-O-acetyl-5'-deoxy-5-fluoro-N4 (neopentyloxycarbonyl)cytidine as pale yellow oil. This crude product was dissolved in ethanol (15 ml) and cooled on ice-bath. Then 1N aqueous sodium hydroxide solution was added dropwise while maintaining the temperature below 15° C. After the addition was completed, the reaction mixture was neutralized with concentrated. hydrochloric acid at 0° C. The solution was concentrated under reduced pressure, and the concentrate was partitioned between water and a mixed solution of CH2Cl 2 /MeOH (95:5). The aqueous layer was back-extracted with CH2Cl2 /MeOH (95:5) ten times (20 ml each). All organic layers were combined, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography using CH2Cl2 /MeOH (20:1) as an eluent to give 5'-deoxy-5-fluoro-N4 -(neopentyloxycarbonyl)cytidine (1.37 g: 84% yield) as amorphous powder: FAB-MS m/z 360 (MH+); 1H-NMR (d6 -DMSO) δ0.93 (9H, s), 1.31 (3H, d,J=6.3 Hz), 3.68 (1H,q,J=5.9 Hz), 3.81 (2H, br. s), 3.87-3.92 (1H, m), 4.04-4.09 (1H, m), 5.05 (1H,d,J=5.9 Hz), 5.41 (1H, br. d, J=5.3 Hz), 5.67 (1H,dd,J=1.3, 3.6 Hz), 8.04 (1H, br. s), 10.53 (~1H, br. s).

1. customAfter the solvent was removed under reduced pressure
2. customthe residue was partitioned between ether and saturated aqueous solution of sodium carbonate
3. washThe organic layer was successively washed with water and brine
4. dry with materialdried over anhydrous sodium sulfate
5. concentrationconcentrated under reduced pressure