Thymine → 1-Ethylthymine

To a stirring suspension of thymine (551 mg, 3.32 mmol) in dry DMF (3 mL) was added sodium hydride (60% oil dispersion, 133 mg, 3.32 mmol). After stirring the mixture for 30 min at room temperature, a solution of cis-5-bromomethyl-2-diethoxyphosphinoyl-tetrahydrofuran (example 66) (500 mg, 1.66 mmol) in DMF (3 mL) was added via cannula. The mixture was then stirred at 90° C. for 15 h after which the mixture was cooled and quenched with saturated ammonium chloride (5 mL). The volatiles were removed under vacuo and the residue was dissolved in a mixture of dichloromethane (20 mL) and water (10 mL). The mixture was filtered and the aqueous layer was collected and extracted with dichloromethane (2×20 mL). The combined extracts were then washed with brine (20 mL), dried (MgSO4) and concentrated to dryness. Purification by chromatography eluting with EtAc, 5% MeOH in EtAc then 10% MeOH in EtAc yielded first N1-ethyl thymine (102 mg, 40%) and then the title compound as an oil (126 mg, 22%).

1. stirringThe mixture was then stirred at 90° C. for 15 h after which the mixture
2. temperaturewas cooled
3. customquenched with saturated ammonium chloride (5 mL)
4. customThe volatiles were removed under vacuo
5. dissolutionthe residue was dissolved in a mixture of dichloromethane (20 mL) and water (10 mL)
6. filtrationThe mixture was filtered
7. customthe aqueous layer was collected
8. extractionextracted with dichloromethane (2×20 mL)
9. washThe combined extracts were then washed with brine (20 mL)
10. dry with materialdried (MgSO4)
11. concentrationconcentrated to dryness
12. customPurification by chromatography
13. washeluting with EtAc, 5% MeOH in EtAc

ORD record

ord-71072d6585bf4706a0bf1a4527e542a6

Source dataset

uspto-grants-2001_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06194576B1