Fumaric Acid → Tenofovir Disoproxil Fumarate

HRID 16919Notes

Reaction equation

HRID 16919 reaction equation
[CH3:1][C@@H:2]([O:14][CH2:15][P:16]([O:27][CH2:28][O:29][C:30]([O:32][CH:33]([CH3:35])[CH3:34])=[O:31])([O:18][CH2:19][O:20][C:21]([O:23][CH:24]([CH3:26])[CH3:25])=[O:22])=[O:17])[CH2:3][N:4]1[C:8]2[N:9]=[CH:10][N:11]=[C:12]([NH2:13])[C:7]=2[N:6]=[CH:5]1.[C:36]([OH:43])(=[O:42])/[CH:37]=[CH:38]/[C:39]([OH:41])=[O:40]>C(O)(C)C>[CH3:1][C@@H:2]([O:14][CH2:15][P:16]([O:18][CH2:19][O:20][C:21]([O:23][CH:24]([CH3:26])[CH3:25])=[O:22])([O:27][CH2:28][O:29][C:30]([O:32][CH:33]([CH3:34])[CH3:35])=[O:31])=[O:17])[CH2:3][N:4]1[C:8]2[N:9]=[CH:10][N:11]=[C:12]([NH2:13])[C:7]=2[N:6]=[CH:5]1.[CH:37](/[C:36]([OH:43])=[O:42])=[CH:38]\[C:39]([OH:41])=[O:40]

Participants

4

Reactant 2

HCID 444972Fumaric AcidHCID 5481350Tenofovir Disoproxil

Product 1

HCID 6398764Tenofovir Disoproxil FumarateYield 78.5%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
45 °C

Procedure

Tenofovir disoproxil (2.5 gm) is dissolved in isopropyl alcohol (12.5 ml), fumaric acid (0.6 gm) is added at 25-30° C. and then the temperature is raised to 45° C., maintained for 20 minutes. The reaction mass is cooled to 25-30° C. and stirred for 1 hour at the same temperature and again mass is cooled to 0-5° C., stirred for 1 hour at 0-5° C. Filtered the material, washed with isopropyl alcohol (2 ml) and finally washed with hexane to give 2.4 gm of tenofovir disoproxil fumarate (HPLC Purity: 99.8%).

Workup

  1. temperaturemaintained for 20 minutes
  2. temperatureThe reaction mass is cooled to 25-30° C.
  3. temperatureis cooled to 0-5° C.
  4. stirringstirred for 1 hour at 0-5° C
  5. filtrationFiltered the material
  6. washwashed with isopropyl alcohol (2 ml)
  7. washfinally washed with hexane

Sources & evidence

ORD record
ord-d9db8be4eb924b3caddc5b9408d94f3f
Source dataset
uspto-grants-2010_06
Patent number
US07737273B2

Reaction notes

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