Azobisisobutyronitrile → HCID 11092221, compound

Participants

Reaction Conditions

Reaction Steps

The following preparation should to be performed under a hood and all precautions taken not to inhale any of reagent fumes. A suspension of 3'-deoxy-3'-iodo-5'-O-tritylthymidine (Verheyden, et al., J. Org. Chem. 1970, 35, 2868) (60 g, 0.1 mol), hexamethylditin (36 g, 22.7 ml, 0.11 mol), t-butylisocyanide (166 g, 225 ml, 2 mol), and AIBN (1.6 g, 10 mmol) in toluene (freshly distilled over Na/benzophenone, 2 lt) was thoroughly deoxygenated by bubbling argon through the reaction mixture for 30 min. and then heated at 80° C. for 13 h. The reaction mixture was cooled at 60° C. and AIBN (1.6 g, 10 mmol) was added and heating continued for 24 h. During this period addition of AIBN was repeated for 3 times in an identical manner. The reaction mixture was cooled to room temperature and transferred on the top of a prepacked silica gel column (1.5 kg, in hexanes) and eluted with hexanes: Et2O (100% hexanes→100% Et2O with a 10% gradient change each time using 1 lt of eluent). Most of the impurities were removed during the gradient elution as non-polar compounds. Final elution with Et2O (2 lt), pooling and evaporation of appropriate fractions gave two compounds in the order these were collected. (i) 12.93 g (25%) of 3'-C-Cyano-3'-deoxy-5'-O-tritylthymidine as white powder (crystallized from toluene/Et2O, mp 153°-157° C.); 1H NMR (CDCl3) δ 8.83 (s, 1, NH), 7.04-7.4 (m, 18.5, TrH, C6H, and 0.5 ArH from toluene), 6.10 (dd, 1, H1', J1',2' =4.1 Hz, J1',2" =7.1 Hz), 4.20 (m, 1 , H4', J3',4' =8.4 Hz, J4',5' =2.8 Hz), 3.33-3.60 (m, 3, H5', 5", 3'), 2.68 (m, 1, H2', J2', 2" =13.8 Hz), 2.52 (m, 1, H2"), 2.28 (s, 1.5, 0.5 CH3 from toluene), and 1.50 (s, 3, CH3).

Provenance & Evidence