Ethanol → HCID 54475718, compound

HRID 728758Notes

Reaction equation

HRID 728758 reaction equation
[CH3:1][C:2]1[C:8](=[O:9])[NH:7][C:5](=[O:6])[N:4]([C@@H:10]2[O:14][C@H:13]([CH2:15][OH:16])[C@@H:12]([N:17]=[N+:18]=[N-:19])[CH2:11]2)[CH:3]=1.C(O)C.C[O-].[Na+].Br[CH2:27][C:28]([OH:30])=[O:29]>O.C(Cl)(Cl)Cl.CO.CC(O)=O>[C:28]([CH2:27][N:7]1[C:8](=[O:9])[C:2]([CH3:1])=[CH:3][N:4]([C@@H:10]2[O:14][C@H:13]([CH2:15][OH:16])[C@@H:12]([N:17]=[N+:18]=[N-:19])[CH2:11]2)[C:5]1=[O:6])([OH:30])=[O:29]

Participants

7

Reactant 4

HCID 702EthanolHCID 6227Bromoacetic AcidHCID 35370ZidovudineHCID 10942334Sodium Methoxide2×

Product 1

HCID 54475718HCID 54475718, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 21866353chloroform methanol HOAcSolvent

Procedure

A mixture of 560 mg AZT, 15 ml absolute ethanol, 2 ml sodium methoxide solution (4.4M NaOMe in MeOH) and 500 mg bromoacetic acid was refluxed for5.5 hours, then allowed to stand overnight at room temperature. The next morning, 1 ml NaOMe solution was added followed by 300 mg bromoacetic acidand the mixture refluxed for one hour, at which time the reaction was shownto be complete by TLC on silica gel-F 250 um using the solvent system CHCl3 /MeOH/HOAc (85+15+1). The reaction mixture was diluted with five volumes of deionized water and extracted with CHCl3. The aqueousphase was acidified with 1N HCl, and extracted into EtOAc. The EtOAc extract was concentrated under reduced pressure and chromatographed by preparative TLC on silica gel-F 1000 um using the solvent system CHCl3 /MeOH/HOAc (85+15+1). The product band (Rf =0.25) was scraped, eluted with MeOH and concentrated to a syrup which was flashed repeatedly with CHCl3, MeCl2 and THF until the odor of HOAc was no longer detectable. The oil was stored in vacuo over sodium hydroxide pellets. The product was homogeneous on TLC and its UV spectrum resembled that of AZT-3-VA (Example 2) and 3-methylthymidine. The product was subsequently shown to have immunological activity with antisera to AZT by FPIA.

Workup

  1. temperaturewas refluxed for5
  2. custom5 hours
  3. temperaturerefluxed for one hour, at which time the reaction
  4. extractionextracted with CHCl3
  5. extractionextracted into EtOAc
  6. extractionThe EtOAc extract
  7. concentrationwas concentrated under reduced pressure
  8. customchromatographed by preparative TLC on silica gel-F 1000 um
  9. washeluted with MeOH
  10. concentrationconcentrated to a syrup which

Sources & evidence

ORD record
ord-f4b9f1fd9b3f49d7828d8456701beed1
Source dataset
uspto-grants-1991_09
Patent number
US05051361

Reaction notes

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