Triphenylphosphine → 3'-o-Aminothymidine

Participants

Reaction Steps

Hydrazine monohydrate (7 mL) is added to a suspension of 5′-O-trityl-3′-O-phthalimido-thymidine (2.9 g; ca. 3 mmol nucleoside, contaminated with some Ph3P═O) in ethanol (30 mL), and the solution is heated under reflux for 2 h. The ethanol is removed in vacuo and the resulting mixture is partitioned between CH2Cl2 (100 mL) and aqueous NaCl (50% sat.; 100 mL). The organic phase is separated and concentrated in vacuo to give a colorless foam, which is redissolved in anhydrous dichloromethane (20 mL). A solution of zinc chloride etherate (1 M in Et2O; 30 mL; 30 mmol) is then added. After a few minutes, the product starts to precipitate. After 30 minutes, the solution is diluted with CH2Cl2 (100 mL) and the precipitate removed by filtration. The solids are partitioned between water (20 mL) and CH2Cl2 (20 mL). The aqueous phase is separated and lyophilized. The crude product is purified by reverse phase HPLC(C18, gradient 0-5% acetonitrile in water over 20 minutes) to give 3′-O-amino-thymidine (expected 340 mg; 44% overall) as a colorless foam. 1H-NMR (DMSO-d6; 300 MHz): δ(ppm)=1.77 (d, J=0.7 Hz, 3H); 1.97-2.07 (m, 1H); 2.29 (ddd, J=0.7, 5.9, 13.7 Hz, 1H); 3.50-3.66 (m, 2H); 3.99-4.03 (m, 1H); 4.16-4.20 (m, 1H); 5.08 (t, J=5.1 Hz, 1H); 6.10-6.16 (m, 3H); 7.73 (d, J=1.0 Hz, 1H); 11.27 (br s, 1H). 13C-NMR (DMSO-d6; 75 MHz): a (ppm)=12.3, 35.7, 62.1, 83.7, 83.7, 83.9, 109.5, 136.0, 150.5, 163.7.

Provenance & Evidence