Sodium Hydroxide → N4-benzoyl-2'-fluoro-3'-(4-methoxytrityl)amino-2',3'-dideoxycytidine

Participants

Reaction Steps

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).

Provenance & Evidence