تفاعل #58428

معادلة التفاعل

trimethylsilyl triflate

6-chloropurine

ammonium sulfate

sodium bicarbonate

6

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

→

7

المردود 82.0%

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

المردود 82.0%

المذيبات

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

dichloromethane

acetonitrile

ظروف التفاعل

المعالجة

1. 1
   درجة الحرارةwas refluxed for 3 h
2. 2
   أخرىthe solvent was removed in vacuo at 35-40° C
3. 3
   أخرىThe organic layer was separated
4. 4
   استخلاصthe aqueous phase was extracted with dichloromethane (2×100 mL)
5. 5
   غسيلThe combined organic extracts were washed with water (50 mL), brine (50 mL)
6. 6
   تجفيفdried over magnesium sulfate
7. 7
   ترشيحfiltered
8. 8
   تركيزconcentrated to a crude that
9. 9
   أخرىwas purified by tlc-grade silica gel flash chromatography (1:49 methanol/dichloromethane)

الإجراء التجريبي

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.

المصدر