反应详情

N4 -benzoyl-2'-fluoro-3'-(4-methoxytrityl)amino-2',3'-dideoxycytidine 15 was prepared as follows: To 1.3 g (1.75 mmol) of 14 in 20 mL of 65/30/5 pyridine/methanol/water, cooled in an ice bath, was added 10 mL of cold 2M NaOH in 65/30/5 pyridine/methanol/water. The mixture was stirred cold for 20 min, then neutralized with pyridinium-H+ form Bio-Rad AG® 50W-X8 cation exchange resin. After 5 min, the resin was removed by filtration and washed with methanol. The combined filtrate and wash were concentrated in vacuo to an oil, which was dissolved in 100 mL ethyl acetate. The mixture was washed with 100 mL saturated aqueous NaHCO3 and with water (2×100 mL). After concentration in vacuo to a foam, the product was dissolved in 10 mL CH2Cl2 and pipetted into 75 mL rapidly stirred hexane/ether, 2/1. The product was collected by filtration and dried under vacuum, giving 1.13 g (102% yield) of product as a white powder. Mass-spectrometry, FAB+, M+Cs+, calculated: 753.1489, observed: 753.1499. 1H NMR δ 8.30 (br d, J=6.8 Hz, 1H), 7.89 (br d, J=6.7 Hz, 2H), 7.64 (dd, J=7.4, 7.4 Hz, 1H), 7.44-7.56 (mm, 9H), 7.22-7.32 (mm, 9H), 6.82 (d, J=8.8Hz, 2H), 5.80 (d, J=15.7Hz, 1H), 4.26 (mm, 2H), 4.13 (d, J=10.2 Hz, 1H), 3.81 (s, 3H), 3.26 (dddd, J=3.4, 10.7, 10.8, 26.5 Hz, 1H), 2.93 (dd, J =3.3, 50.5 Hz, 1H), 2.50 (dd, J=2.8, 11.0 Hz, 1H); 19F NMR δ -195.3 (m).

1. customform Bio-Rad AG® 50W-X8 cation exchange resin
2. waitAfter 5 min
3. customthe resin was removed by filtration
4. washwashed with methanol
5. washThe combined filtrate and wash
6. concentrationwere concentrated in vacuo to an oil, which
7. dissolutionwas dissolved in 100 mL ethyl acetate
8. washThe mixture was washed with 100 mL saturated aqueous NaHCO3 and with water (2×100 mL)
9. concentrationAfter concentration in vacuo to a foam
10. dissolutionthe product was dissolved in 10 mL CH2Cl2
11. filtrationThe product was collected by filtration
12. customdried under vacuum