Ethanol → 1-(3-O-Benzyl-2-deoxypentofuranosyl)-4-hydroxy-5-(trifluoromethyl)pyrimidin-2(1H)-one

Temperature

5 °C

To a stirred mixture of 3.5 g (0.01 mole) of methyl 3-O-benzyl-5-O-(t-butyldimethylsilyl)-2-deoxyribofuranoside and 3.4 g (0.01 mole) of Bis-(trimethylsilyl-5-trifluoromethyluracil in 30 ml of methylene chloride at <5° C. was added a solution of 2.9 g (0.011 mole) of stannic chloride in 5 ml of methylene chloride at ca. 0.25 ml/min. The clear yellow solution was stirred for an additional one and one-half hours at 5° C. during which time the color darkened and a fine precipitate formed. Anhydrous ethanol (11 ml) was then added to the mixture. After warming to ambient temperature, the mixture was filtered removing only a small amount of a solid material. The solvent was then removed under vacuum. The dark residual oil was triturated (3×50 ml) with hexane. The residue was taken up in 100 ml of ethyl acetate, washed with 100 ml of cold saturated sodium bicarbonate solution forming an emulsion. This was vacuum filtered and the filtrate layers separated. The organic phase was washed (2×100 ml) with DI water, dried (Na2SO4), filtered, and the solvent removed under vacuum affording 1.0 g of a thick yellow oil. This material was chromatographed on 75 cc of silica gel eluting with ethyl acetate/hexane (1:1). From early eluting fractions, 150 mg (0.39 mmole, 3.9%) of crude beta-anomer of the title product was obtained with 200 mg (0.52 mmole, 5.2%) of the alpha-anomer being found in later eluting fractions. The products were identified by thin layer chromatography and 1H NMR analysis.

1. customa fine precipitate formed
2. temperatureAfter warming to ambient temperature
3. filtrationthe mixture was filtered
4. customremoving only a small amount of a solid material
5. customThe solvent was then removed under vacuum
6. customThe dark residual oil was triturated (3×50 ml) with hexane
7. washwashed with 100 ml of cold saturated sodium bicarbonate solution
8. customforming an emulsion
9. filtrationThis was vacuum filtered
10. customthe filtrate layers separated
11. washThe organic phase was washed (2×100 ml) with DI water
12. dry with materialdried (Na2SO4)
13. filtrationfiltered
14. customthe solvent removed under vacuum

ORD record

ord-09a02fcd9db149229df3a087dffff3eb

Source dataset

uspto-grants-1990_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04898936