Acetyl chloride → Thymidine, 3'-azido-3'-deoxy-, 5'-acetate

HRID 2248850Notes

Reaction equation

HRID 2248850 reaction equation
[N:1]([C@@H:4]1[C@@H:8]([CH2:9][OH:10])[O:7][C@@H:6]([N:11]2[CH:19]=[C:17]([CH3:18])[C:15](=[O:16])[NH:14][C:12]2=[O:13])[CH2:5]1)=[N+:2]=[N-:3].[C:20](Cl)(=[O:22])[CH3:21]>N1C=CC=CC=1>[C:20]([O:10][CH2:9][C@H:8]1[O:7][C@@H:6]([N:11]2[CH:19]=[C:17]([CH3:18])[C:15](=[O:16])[NH:14][C:12]2=[O:13])[CH2:5][C@@H:4]1[N:1]=[N+:2]=[N-:3])(=[O:22])[CH3:21]

Participants

4

Reactant 2

HCID 6367Acetyl chlorideHCID 35370Zidovudine

Product 1

HCID 452423Thymidine, 3'-azido-3'-deoxy-, 5'-acetate

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

To a solution of 3'-azido-3'-deoxythymidine (AZT) 20 g) in pyridine (50 mL) at ambient temperature, acetyl chloride (2.1 equivalents) was added. The reaction was stirred for two hours and kept at 0° at 5° C. for 20 hours. It was poured onto ice water with stirring. The aqueous phase was decanted. The oily product was dissolved in ethyl acetate and extracted with water (5 times), 0.5 N hydrochloric acid, water (2x), and dried over magnesium sulphate. The solution was filtered and evaporated in vacuo. The residual oil was dissolved in chloroform, applied to a silica gel column, and flash chromatographed using 2% methanol in chloroform. Fractions with product were evaporated and the oil was chromatographed again using ethyl acetate:hexane (6:4 v/v). Fractions with product were evaporated in vacuo to give 5'-O-acetyl-3'-azido-3'-deoxythymidine as a white solid.

Workup

  1. waitkept at 0° at 5° C. for 20 hours
  2. additionIt was poured onto ice water
  3. stirringwith stirring
  4. customThe aqueous phase was decanted
  5. dissolutionThe oily product was dissolved in ethyl acetate
  6. extractionextracted with water (5 times), 0.5 N hydrochloric acid, water (2x)
  7. dry with materialdried over magnesium sulphate
  8. filtrationThe solution was filtered
  9. customevaporated in vacuo
  10. dissolutionThe residual oil was dissolved in chloroform
  11. customchromatographed
  12. customFractions with product were evaporated
  13. customthe oil was chromatographed again using ethyl acetate:hexane (6:4 v/v)
  14. customFractions with product were evaporated in vacuo

Sources & evidence

ORD record
ord-af3bb7e1c2bb4055a0fd7e2b569f9be4
Source dataset
uspto-grants-1991_08
Patent number
US05041543

Reaction notes

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