Hydrogen Bromide → Tenofovir

HRID 554464

Reaction equation

C([C:3](CC)([P:18]([OH:21])([OH:20])=[O:19])[O:4][C@H:5]([CH3:17])[CH2:6][N:7]1[CH:15]=[N:14][C:13]2[C:8]1=[N:9][CH:10]=[N:11][C:12]=2[NH2:16])C.Br>C(O)(=O)C.Cl.CC(O)C>[P:18]([CH2:3][O:4][C@H:5]([CH3:17])[CH2:6][N:7]1[CH:15]=[N:14][C:13]2[C:8]1=[N:9][CH:10]=[N:11][C:12]=2[NH2:16])([OH:20])([OH:21])=[O:19]

Participants

Conditions

Temperature: 92.5 °C

Procedure

Dealkylation of (R)-9-[2-(Diethyl phosphonomethoxy)propyl]adenine is carried out in presence of a suitable dealkylating reagents selected from mineral acids like aq. HBr, aq. HCl, HBr in acetic acid or HCl gas in IPA with mole ratio ranging from 3 to 15 preferably 7.5 moles and typically at a temperature of about 25 to 110° C., usually at 90 to 95° C. (R)-9-[2-(Diethyl phosphonomethoxy)propyl]adenine and one of the acid described above are maintained at 90 to 95° C. for about 3 to 15 hrs, after completion of reaction, the reaction mass is washed with Methylenedichloride and pH is adjusted to about 1.5 to 3.5 preferably at 2.5 to 3.0 with caustic lye solution. Reaction mass is cooled to about 25 to 35° C. and finally to about 0 to 5° C. over 4 to 10 hrs. The precipitated product is filtered and the wet material is recrystallized in water to get pure (R)-9-[2-(phosphonomethoxy)propyl]adenine with improved yield.

Workup

customranging from 3 to 15 preferably 7.5 moles and typically at a temperature of about 25 to 110° C., usually at 90 to 95° C.
customafter completion of reaction
washthe reaction mass is washed with Methylenedichloride and pH
customReaction mass
temperatureis cooled to about 25 to 35° C. and finally to about 0 to 5° C. over 4 to 10 hrs
filtrationThe precipitated product is filtered
customthe wet material is recrystallized in water

Sources & evidence

ORD record: ord-9dd785a1580b4faa80fdcfc77899ff12
Source dataset: uspto-grants-2011_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08049009B2

Linked notes

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