Реакция #53954

Уравнение реакции

Benzenesulfonic acid

sodium hydride

1-[5-[bis-(4-methoxy-phenyl)-phenyl-methoxymethyl]-3,4-bis-(tert-butyl-dimethyl-silanyloxy)-tetrahydro-furan-2-yl]-1H-pyrimidine-2,4-dione

p-methoxybenzyl chloride

→

1-[(2R,3R,4R,5R)-3,4-bis{[tert-butyl(dimethyl)silyl]oxy}-5-(hydroxymethyl)tetrahydro-2-furanyl]-3-(4-methoxybenzyl)-2,4(1H,3H)-pyrimidinedione

Выход 59.0%

Растворители

ethyl acetate

ethyl acetate

dimethylformamide

dimethylformamide

Условия реакции

Обработка

1. 1
   ПромывкаThe organic layer was washed with saturated sodium bicarbonate aqueous solution and saturated sodium chloride solution
2. 2
   Сушкаdried over magnesium sulfate
3. 3
   Фильтрацияfiltered
4. 4
   Концентрированиеconcentrated to dryness in vacuo
5. 5
   workup.DISSOLUTIONThe oily residue was dissolved in chloroform (200 ml)
6. 6
   Температураcooled at 0° C. under nitrogen
7. 7
   workup.STIRRINGthe resulting red solution was stirred at 0° C. under nitrogen for 2 h
8. 8
   ПромывкаThe organic layer was washed with saturated sodium bicarbonate aqueous solution and saturated sodium chloride solution
9. 9
   Сушкаdried over magnesium sulfate
10. 10
    Фильтрацияfiltered
11. 11
    Концентрированиеconcentrated to dryness in vacuo
12. 12
    ДругоеThe residue was chromatographed (flash column, silica gel, methylene chloride:diethyl ether:methanol=95:3:2)

Методика

Following the procedure (Myers, A. G.; Gin, D. Y.; Rogers, D. H., J. Amer. Chem. Soc., 1994, 116, 4697-4718), a suspension of sodium hydride (1.55 g, 38.75 mmole, 60% oil dispersion) in anhydrous dimethylformamide (40 ml) was cooled at 0° C. under argon, and to this mixture was added a solution of 1-[5-[bis-(4-methoxy-phenyl)-phenyl-methoxymethyl]-3,4-bis-(tert-butyl-dimethyl-silanyloxy)-tetrahydro-furan-2-yl]-1H-pyrimidine-2,4-dione (20 g, 25.8 mmole, obtained from Reference Example 1) in anhydrous dimethylformamide (35 ml) over a period of 15 min. Neat p-methoxybenzyl chloride (7 ml, 51 mmole) was added to this solution. The resulting mixture was stirred at 0° C. for 15 h under argon, and diluted with ethyl acetate (700 ml). The organic layer was washed with saturated sodium bicarbonate aqueous solution and saturated sodium chloride solution, dried over magnesium sulfate, filtered and concentrated to dryness in vacuo. The oily residue was dissolved in chloroform (200 ml) and cooled at 0° C. under nitrogen. Benzenesulfonic acid (6 g, 37.93 mmole) was added portionwise, and the resulting red solution was stirred at 0° C. under nitrogen for 2 h. The mixture was diluted with ethyl acetate. The organic layer was washed with saturated sodium bicarbonate aqueous solution and saturated sodium chloride solution, dried over magnesium sulfate, filtered and concentrated to dryness in vacuo. The residue was chromatographed (flash column, silica gel, methylene chloride:diethyl ether:methanol=95:3:2) to give 1-[(2R,3R,4R,5R)-3,4-bis{[tert-butyl(dimethyl)silyl]oxy}-5-(hydroxymethyl)tetrahydro-2-furanyl]-3-(4-methoxybenzyl)-2,4(1H,3H)-pyrimidinedione as white solid (9 g, 59%).

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