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

HRID 629930Notes

Reaction equation

[NH2:1][C:2]1[N:10]=[C:9](Cl)[N:8]=[C:7]2[C:3]=1[N:4]=[CH:5][N:6]2[CH2:12][C:13]1[CH:27]=[CH:26][C:16]([CH2:17][P:18](=[O:25])([O:22][CH2:23][CH3:24])[O:19][CH2:20][CH3:21])=[CH:15][CH:14]=1.[H-].[Na+].[CH3:30][O:31][CH2:32][CH2:33][OH:34]>O.CCOC(C)=O>[NH2:1][C:2]1[N:10]=[C:9]([O:34][CH2:33][CH2:32][O:31][CH3:30])[N:8]=[C:7]2[C:3]=1[N:4]=[CH:5][N:6]2[CH2:12][C:13]1[CH:27]=[CH:26][C:16]([CH2:17][P:18](=[O:25])([O:22][CH2:23][CH3:24])[O:19][CH2:20][CH3:21])=[CH:15][CH:14]=1

Participants

Conditions

Temperature: 120 °C

Procedure

To a solution of diethyl 4-((6-amino-2-chloro-9H-purin-9-yl)methyl)benzylphosphonate (1 equiv.) in 2-methoxyethanol (0.10 M) was added sodium hydride (1.3 equiv.). The reaction mixture was then heated to 120° C. for 18 h. At this point the reaction mixture was allowed to cool to room temperature. The mixture was then diluted with water and EtOAc. This mixture was transferred to a separatory funnel and washed with water three times. The organic layer was then separated, dried over anhydrous Na2SO4 and the volatiles were removed in vacuo. The resulting residue was purified by a COMBIFLASH™ system using a gradient of 0-10% MeOH/DCM to provide the title compound in quantitative yield as a solid.

Workup

temperatureto cool to room temperature
customThis mixture was transferred to a separatory funnel
washwashed with water three times
customThe organic layer was then separated
dry with materialdried over anhydrous Na2SO4
customthe volatiles were removed in vacuo
customThe resulting residue was purified by a COMBIFLASH™ system

Sources & evidence

ORD record: ord-9bcd1f1eef8c43ddb1d25a9bf116d9a3
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09315530B2

Reaction notes

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