Azobisisobutyronitrile → HCID 11092221, compound

HRID 1770337Notes

Reaction equation

HRID 1770337 reaction equation
I[C@@H:2]1[C@@H:6]([CH2:7][O:8][C:9]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[O:5][C@@H:4]([N:28]2[CH:36]=[C:34]([CH3:35])[C:32](=[O:33])[NH:31][C:29]2=[O:30])[CH2:3]1.C[Sn](C)C.C[Sn](C)C.[C:45]([N+:49]#[C-])(C)(C)C.CC(N=NC(C#N)(C)C)(C#N)C>C1(C)C=CC=CC=1>[C:45]([C@@H:2]1[C@@H:6]([CH2:7][O:8][C:9]([C:22]2[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=2)([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=2)[O:5][C@@H:4]([N:28]2[CH:36]=[C:34]([CH3:35])[C:32](=[O:33])[NH:31][C:29]2=[O:30])[CH2:3]1)#[N:49]

Participants

6

Reactant 4

HCID 6547Azobisisobutyronitrile3×HCID 23577Tert-Butyl isocyanideHCID 6327618HexamethylditinHCID 111039343'-deoxy-3'-iodo-5'-O-tritylthymidine

Product 1

HCID 11092221HCID 11092221, compound

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

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).

Workup

  1. customThe following preparation should
  2. distillationfreshly distilled over Na/benzophenone, 2 lt)
  3. customwas thoroughly deoxygenated
  4. customby bubbling argon through the reaction mixture for 30 min.
  5. temperatureThe reaction mixture was cooled at 60° C.
  6. temperatureheating
  7. temperatureThe reaction mixture was cooled to room temperature
  8. washeluted with hexanes
  9. customMost of the impurities were removed during the gradient elution as non-polar compounds
  10. washFinal elution
  11. customwith Et2O (2 lt), pooling and evaporation of appropriate fractions
  12. customgave two compounds in the order
  13. customthese were collected
  14. custom(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.)

Sources & evidence

ORD record
ord-03118e2b48fa41b1bc4e0594335e0458
Source dataset
uspto-grants-1995_01
Patent number
US05386023

Reaction notes

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