Bromine → diethyl 4-((6-amino-8-bromo-2-(2-methoxyethoxy)-9H-purin-9-yl)methyl)benzylphosphonate

HRID 629931Notes

Reaction equation

HRID 629931 reaction equation
[NH2:1][C:2]1[N:10]=[C:9]([O:11][CH2:12][CH2:13][O:14][CH3:15])[N:8]=[C:7]2[C:3]=1[N:4]=[CH:5][N:6]2[CH2:16][C:17]1[CH:31]=[CH:30][C:20]([CH2:21][P:22](=[O:29])([O:26][CH2:27][CH3:28])[O:23][CH2:24][CH3:25])=[CH:19][CH:18]=1.C([O-])(=O)C.[Na+].[Br:37]Br>C(O)(=O)C>[NH2:1][C:2]1[N:10]=[C:9]([O:11][CH2:12][CH2:13][O:14][CH3:15])[N:8]=[C:7]2[C:3]=1[N:4]=[C:5]([Br:37])[N:6]2[CH2:16][C:17]1[CH:31]=[CH:30][C:20]([CH2:21][P:22](=[O:29])([O:23][CH2:24][CH3:25])[O:26][CH2:27][CH3:28])=[CH:19][CH:18]=1

Participants

5

Reactant 3

HCID 24408BromineHCID 517045Sodium AcetateHCID 86667758diethyl 4-((6-amino-2-(2-methoxyethoxy)-9H-purin-9-yl)methyl)benzylphosphonate

Product 1

HCID 86667760diethyl 4-((6-amino-8-bromo-2-(2-methoxyethoxy)-9H-purin-9-yl)methyl)benzylphosphonateYield 14%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

To a solution of diethyl 4-((6-amino-2-(2-methoxyethoxy)-9H-purin-9-yl)methyl)benzylphosphonate (1 equiv.) in acetic acid (0.20 M) was added sodium acetate (15 equiv.) and bromine (13 equiv.). The reaction mixture was then allowed to stir at room temperature for 18 h. At this point the reaction was quenched by the addition of sodium thiosulfate. The mixture was then diluted with water and DCM. This mixture was transferred to a separatory funnel and washed with DCM three times. The combined organic layers were then dried over anhydrous Na2SO4 and the volatiles were removed in vacuo. The resulting residue was purified by a COMBIFLASH™ system using a gradient of 0-5% MeOH/DCM to provide the title compound (14%) as a solid.

Workup

  1. customAt this point the reaction was quenched by the addition of sodium thiosulfate
  2. additionThe mixture was then diluted with water and DCM
  3. customThis mixture was transferred to a separatory funnel
  4. washwashed with DCM three times
  5. dry with materialThe combined organic layers were then dried over anhydrous Na2SO4
  6. customthe volatiles were removed in vacuo
  7. customThe resulting residue was purified by a COMBIFLASH™ system

Sources & evidence

ORD record
ord-6ffe0737b7204f399e1a37eb3ecbed8d
Source dataset
uspto-grants-2016_04
Patent number
US09315530B2

Reaction notes

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