Thymine → 1-Ethylthymine

To a stirring suspension of thymine (536 mg, 4.18 mmol) in dry DMF (5 mL) was added sodium hydride (60% oil dispersion, 167 mg, 4.18 mmol). After stirring the mixture for 30 min at room temperature, a solution of trans-5-bromomethyl-2-ethoxyphosphinoyl-tetrahydrofuran (example 66) (630 mg, 2.09 mmol) in DMF (3 mL) was added via cannula. The mixture was then stirred at 90° C. for 18 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 (83 mg, 26%) and then the title compound as an oil (186 mg, 26%).

1. stirringThe mixture was then stirred at 90° C. for 18 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-22f2051250b946fabbb023296540dfa8

Source dataset

uspto-grants-2000_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06127540