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With toluene-4-sulfonic acid; In toluene; at 110℃;Large scale;
(1) Add 2700L of anhydrous toluene, 600 kg of diacetylguanine and 15 kg of p-toluenesulfonic acid to the reaction kettle, and heat to reflux.(2) Maintain the temperature at 110 C, add 675L of 2-oxa-1,4-butanediol diacetate, and control the addition for 1 hour.(3) Insulation reflux for about 1 hour.(4) Maintain the reflux reaction, and slowly rectify toluene under normal pressure within 16 hours. The toluene distillation rate is 90 L / h, and 1440 L of toluene is co-distilled.(5) After evaporating toluene for 6 hours, start to add about 900L of anhydrous toluene at a rate of 90L / h.(6) After the reaction was completed, the temperature was lowered to below 30 C and centrifuged, and the obtained solid was dried at 105 C to obtain 744.0 kg of diacetyl acyclovir with a yield of 94.3% and a HPLC detection content of 99.2%.