Dimethylformamide → Tenofovir

HRID 554463

Reaction equation

HRID 554463 reaction equation
[OH:1][C@H:2]([CH3:14])[CH2:3][N:4]1[CH:12]=[N:11][C:10]2[C:5]1=[N:6][CH:7]=[N:8][C:9]=2[NH2:13].CC[O:17][P:18]([O:32]CC)([CH2:20]OS(C1C=CC(C)=CC=1)(=O)=O)=[O:19].CC(C)([O-])C.[Mg+2].CC(C)([O-])C.CN(C)C=O>O.C(Cl)CCl.C(Cl)(Cl)Cl.C(Cl)Cl.C(O)(=O)C>[P:18]([CH2:20][O:1][C@H:2]([CH3:14])[CH2:3][N:4]1[CH:12]=[N:11][C:10]2[C:5]1=[N:6][CH:7]=[N:8][C:9]=2[NH2:13])([OH:32])([OH:19])=[O:17]

Participants

10

Reactant 4

HCID 6228DimethylformamideHCID 4452119-(2-Hydroxypropyl)adenine, (R)-HCID 4193599Diethyl P-[[[(4-methylphenyl)sulfonyl]oxy]methyl]phosphonateHCID 12040442Magnesium 2-methylpropan-2-olate

Product 1

HCID 464205Tenofovir

Reagents, catalysts & solvents 5

HCID 111,2-DichloroethaneSolventHCID 176Acetic AcidSolventHCID 962WaterSolventHCID 6212ChloroformSolventHCID 6344DichloromethaneSolvent

Procedure

Accordingly (R)-9-[2-(hydroxyl)propyl]adenine is condensed with Diethyl p-toluene sulfonyloxy methylphosphonate in presence of Magnesium tert-butoxide in a polar solvent preferably dimethylformamide at a temperature of 70° C. to 80° C. After the reaction completion the reaction mass is neutralized by adding an acid preferably acetic acid and the solvent is distilled off completely. The obtained crude is dissolved in a chlorinated hydrocarbon selected from Methylenedichloride, chloroform, and Ethylene dichloride and water is added. The reaction mixture is filtered to remove the salts and Methylenedichloride layer is separated. Methylenedichloride is distilled off completely to get (R)-9-[2-(phosphonomethoxy)propyl]adenine.

Workup

  1. distillationthe solvent is distilled off completely
  2. customThe obtained crude
  3. additionis added
  4. filtrationThe reaction mixture is filtered
  5. customto remove the salts and Methylenedichloride layer
  6. customis separated
  7. distillationMethylenedichloride is distilled off completely

Sources & evidence

ORD record
ord-1c01f1b6a05443549967b3ba56551380
Source dataset
uspto-grants-2011_11
Patent number
US08049009B2

Linked notes

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