Dimethyl Sulfoxide → 5'-Carbethoxymethylene-3'-azido-5',3'dideoxythymidine

HRID 443001

Reaction equation

HRID 443001 reaction equation
CS(C)=O.C(Cl)(=O)C(Cl)=O.[N:11]([C@@H:14]1[C@@H:18]([CH2:19]O)[O:17][C@@H:16]([N:21]2[CH:29]=[C:27]([CH3:28])[C:25](=[O:26])[NH:24][C:22]2=[O:23])[CH2:15]1)=[N+:12]=[N-:13].[C:30]([CH:35]=P(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)([O:32][CH2:33][CH3:34])=[O:31]>C(Cl)Cl.CS(C)=O.C(Cl)Cl.C(N(CC)CC)C>[C:30]([CH:35]=[CH:19][C@H:18]1[O:17][C@@H:16]([N:21]2[CH:29]=[C:27]([CH3:28])[C:25](=[O:26])[NH:24][C:22]2=[O:23])[CH2:15][C@@H:14]1[N:11]=[N+:12]=[N-:13])([O:32][CH2:33][CH3:34])=[O:31]

Participants

8

Reactant 4

HCID 679Dimethyl SulfoxideHCID 35370ZidovudineHCID 65578Oxalyl chlorideHCID 70670Acetic acid, 2-(triphenylphosphoranylidene)-, ethyl ester

Product 1

HCID 540692895'-Carbethoxymethylene-3'-azido-5',3'dideoxythymidineYield 76.1%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolvent3×HCID 8471TriethylamineSolventHCID 21912085Dimethylsulfoxide-dichloromethaneSolvent

Procedure

A solution of DMSO(426 μl, 6 mM) in methylene chloride (1.5 ml) was added to a stirred solution of oxalyl chloride (288 μl, 3.3 mM) in methylene chloride (7.6 ml) at -78° C. under nitrogen. After 5 minutes, a solution of 3'-azido-3'-deoxythymidine (801 mg; 3 mM) in DMSO/CH2Cl2 (1.12 ml/3.47 ml) was added over a ten minute period. Stirring was continued for 20 minutes, and then triethylamine (2.09 ml, 15 mM) was added and the reaction mixture was stirred for an additional 5 minutes. (Carbethoxymethylene)triphenylphosphorane (1.57 g; 4.5 mM) was added in a solution of methylene chloride (9 ml), and the reaction mixture was stirred at -78° C. for 30 minutes and then allowed to stand at room temperature for 1 hour. The crude reaction mixture was then quenched with cold water (20 ml) and extracted into ethyl acetate (2×50 ml), washed with brine and dried over anhydrous sodium sulfate. The crude product was purified by flash chromatography (SiO2 : 60 g; 60% ethyl acetate/hexane) to afford 765 mg (76%) of the title compound. Rf -0.47(7/3 EtOAc/Hexane).

Workup

  1. waitwas continued for 20 minutes
  2. stirringthe reaction mixture was stirred for an additional 5 minutes
  3. stirringthe reaction mixture was stirred at -78° C. for 30 minutes
  4. waitto stand at room temperature for 1 hour
  5. customThe crude reaction mixture
  6. customwas then quenched with cold water (20 ml)
  7. extractionextracted into ethyl acetate (2×50 ml)
  8. washwashed with brine
  9. dry with materialdried over anhydrous sodium sulfate
  10. customThe crude product was purified by flash chromatography (SiO2 : 60 g; 60% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-e6a130b2cf6d408f9295352ec7df2aef
Source dataset
uspto-grants-1999_04
Patent number
US05892024

Linked notes

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