Ethyl Acetate → 1-[(Diethylphosphonomethoxy)methoxymethyl]thymine

HRID 1551

Reaction equation

HRID 1551 reaction equation
[C:1]([O:9][CH2:10][O:11][CH2:12][N:13]1[CH:21]=[C:19]([CH3:20])[C:17](=[O:18])[NH:16][C:14]1=[O:15])(=O)C1C=CC=CC=1.C([CH:24]([CH2:30]C)[O:25][P:26]([OH:29])([OH:28])=O)C.FC(F)(F)S(O[Si](C)(C)C)(=O)=O.[C:44](OCC)(=O)[CH3:45]>C1C=CC=CC=1>[CH2:44]([O:29][P:26]([CH2:1][O:9][CH2:10][O:11][CH2:12][N:13]1[CH:21]=[C:19]([CH3:20])[C:17](=[O:18])[NH:16][C:14]1=[O:15])([O:25][CH2:24][CH3:30])=[O:28])[CH3:45]

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 65367Trimethylsilyl triflateHCID 148435351-[(Benzoyloxy)methoxymethyl]thymineHCID 54112757Pentan-3-yl dihydrogen phosphate

Product 1

HCID 148865321-[(Diethylphosphonomethoxy)methoxymethyl]thymine

Reagents, catalysts & solvents 1

HCID 241BenzeneSolvent

Conditions

Temperature
85 °C

Procedure

To a solution of 1-[(benzoyloxy)methoxymethyl]thymine (2.9 g, 10 mmol) and diethyl phosphonomethanol (1.85 g, 11 mmol) in benzene (180 mL) was added trimethylsilyl trifluoromethanesulfonate (0.05 mL) via a syringe under nitrogen. The solution was heated at 85° C. for 20 min. After cooling to room temperature, ethyl acetate (50 mL) was added and washed with aqueous bicarbonate, brine dried (MgSO4), filtered and concentrated in vacuo. The resultant yellow oil was purified by silica gel column chromatography using CH2Cl2 /5% MeOH as an eluent to give the title compound as a white oil: yield 980 mg (30%).

Workup

  1. temperatureAfter cooling to room temperature
  2. washwashed with aqueous bicarbonate, brine
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe resultant yellow oil was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-32e98db4036848ce8b8264c0ec0c3131
Source dataset
uspto-grants-1998_03
Patent number
US05726174

Linked notes

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