Fumaric Acid → Tenofovir Disoproxil Fumarate

HRID 1897527Notes

Reaction equation

HRID 1897527 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 98.1%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
52.5 °C

Procedure

Tenofovir disoproxil (25 kg) was dissolved in isopropyl alcohol (100 liters) at 25-30° C. Fumaric acid (10 kg) was added and the mixture was heated to 50-55° C. for 1 hour, gradually cooled to 25-30° C., further chilled to 10° C. and stirred for 4 hours. The resulting solid was filtered and washed with chilled isopropyl alcohol. The wet cake was stirred in isopropyl acetate (200 ltrs.) at 10-15° C. for 4 hours. The solid was filtered and washed with chilled isopropyl acetate and dried under vacuum to obtain 30 kg of tenofovir disoproxil fumarate.

Workup

  1. temperaturegradually cooled to 25-30° C.
  2. temperaturefurther chilled to 10° C.
  3. filtrationThe resulting solid was filtered
  4. washwashed with chilled isopropyl alcohol
  5. stirringThe wet cake was stirred in isopropyl acetate (200 ltrs.) at 10-15° C. for 4 hours
  6. filtrationThe solid was filtered
  7. washwashed with chilled isopropyl acetate
  8. customdried under vacuum

Sources & evidence

ORD record
ord-d0e5aa4651974d139bedb41cda9d3c9a
Source dataset
uspto-grants-2013_08
Patent number
US08519126B2

Reaction notes

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