反応 #58428

反応方程式

trimethylsilyl triflate

6-chloropurine

ammonium sulfate

sodium bicarbonate

6

5-O-tert-Butyldiphenylsilyl-3-deoxy-1,2-diacetyl-3-fluorenylmethylcarbonylamino-β-L-ribofuranose

→

7

収率 82.0%

9-(2-O-Acetyl-5-O-tert-butyldiphenylsilyl-3-deoxy-3-fluorenylmethylcarbonylamino-β-L-ribofuranosyl)-6-chloropurine

収率 82.0%

溶媒

1,1,1,3,3,3-hexamethyldisilazane

dichloromethane

acetonitrile

反応条件

後処理

1. 1
   温度was refluxed for 3 h
2. 2
   その他the solvent was removed in vacuo at 35-40° C
3. 3
   その他The organic layer was separated
4. 4
   抽出the aqueous phase was extracted with dichloromethane (2×100 mL)
5. 5
   洗浄The combined organic extracts were washed with water (50 mL), brine (50 mL)
6. 6
   乾燥dried over magnesium sulfate
7. 7
   ろ過filtered
8. 8
   濃縮concentrated to a crude that
9. 9
   その他was purified by tlc-grade silica gel flash chromatography (1:49 methanol/dichloromethane)

実験手順

A mixture of 6-chloropurine (0.67 g, 4.33 mmol) and ammonium sulfate (30 mg, 0.23 mmol) in 1,1,1,3,3,3-hexamethyldisilazane (30 mL) was refluxed for 3 h, then the solvent was removed in vacuo at 35-40° C. A solution of 6 (1.88 g, 2.71 mmol) in anhydrous acetonitrile (30 mL) was added to the residual solid. The resulting solution was cooled to 0° C. and trimethylsilyl triflate (0.78 mL, 4.31 mmol) was added, and the reaction was stirred at rt overnight. The resulting solution was diluted to 100 mL with dichloromethane and slowly added to an ice-cold saturated solution of sodium bicarbonate (200 mL). The organic layer was separated and the aqueous phase was extracted with dichloromethane (2×100 mL). The combined organic extracts were washed with water (50 mL), brine (50 mL), dried over magnesium sulfate, filtered and concentrated to a crude that was purified by tlc-grade silica gel flash chromatography (1:49 methanol/dichloromethane) to give 7 as a white solid (1.75 g, 82%). Rf0.14 (1:49 methanol/dichloromethane); mp 91-93° C. (dec.); [α]D25 −17.83 (c 0.42, CHCl3); UV (MeOH) λmax 264.0, 299.0; 1H NMR (CDCl3, 400 MHz) δ8.70 (s, 1H), 8.34 (s, 1H), 7.81-7.78 (m, 2H), 7.68-7.57 (m, 6H), 7.44-7.36 (m, 4H), 7.35-7.29 (m, 4H), 7.26-7.22 (m, 2H), 6.15 (s, 1H), 5.67-5.64 (m, 1H), 5.12-5.06 (m, 1H), 4.99-4.95 (m, 1H), 4.55-4.45 (m, 2H), 4.25-4.21 (m, 1H), 4.16-4.12 (m, 1H), 4.03-3.99 (m, 1H), 3.88-3.83 (m, 1H), 2.15 (s, 3H), 1.03 (s, 9H); 13C NMR (CDCl3, 100 MHz) δ 169.4, 152.0, 151.1, 150.8, 143.8, 143.5, 143.4, 141.2, 135.5, 135.3, 132.5, 132.2, 132.0, 129.7, 127.6, 127.5, 126.9, 124.7, 124.6, 119.9, 88.0, 83.2, 75.4, 66.8, 62.8, 50.9, 47.0, 26.6, 20.5, 19.0; Mass ([M+H]+) 788, ([M+Na]+) 810, ([2M+Na]+) 1597. Anal. Calcd for C43H42ClN5O6Si: C, 65.51; H, 5.37; N, 8.88. Found: C, 65.24; H, 5.54; N, 8.56.

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