Sodium hydride → 1-[(Diethylphosphonomethoxy)methoxymethyl]cytosine

HRID 356732Notes

Reaction equation

[H-].[Na+].[NH:3]1[CH:10]=[CH:9][C:7]([NH2:8])=[N:6][C:4]1=[O:5].Cl[CH2:12][O:13][CH2:14][O:15][CH2:16][P:17]([O:22][CH2:23][CH3:24])([O:19][CH2:20][CH3:21])=[O:18]>CN(C=O)C>[CH2:23]([O:22][P:17]([CH2:16][O:15][CH2:14][O:13][CH2:12][N:3]1[CH:10]=[CH:9][C:7]([NH2:8])=[N:6][C:4]1=[O:5])([O:19][CH2:20][CH3:21])=[O:18])[CH3:24]

Participants

Conditions

Temperature: 80 °C

Procedure

To a suspension of 60% sodium hydride in mineral oil (700 mg, 17 mmol) in DMF (50 mL) was added cytosine (1.9 g, 17 mmol) and the mixture was heated at 80° C. for 2 hr under nitrogen. To the resulting yellow solution was added dropwise a solution of chloromethoxy(diethylphosphonomethoxy)methane [prepared from diethylphosphate (2.4 g, 17 mmol) and bis-(chloromethoxy)methane (12.5 g, 86 mmol)] in DMF (10 mL) under nitrogen. After stirring 15 hr at 25° C., the volatiles were removed in vacuo. The residue was dissolved in ethyl acetate (120 mL) and water (30 mL). The organic phase was washed with brine and dried (MgSO4). After removal of the solvent in vacuo, the residual oil was chromatographed on silica gel using CH2Cl2 /10% MeOH as eluent to give the title compound as a white oil: yield 1.2 g (22%).

Workup

customthe volatiles were removed in vacuo
dissolutionThe residue was dissolved in ethyl acetate (120 mL)
washThe organic phase was washed with brine
dry with materialdried (MgSO4)
customAfter removal of the solvent in vacuo
customthe residual oil was chromatographed on silica gel

Sources & evidence

ORD record: ord-358ac4a14ad1447aa1cdb63d77fa8a62
Source dataset: uspto-grants-1998_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US05837871

Reaction notes

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