Acetylation of cannabinol

Abstract

A process for producing THC-O-acetate using a succession of distillation, salting-out assisted liquid-liquid extractions (SALLEs), and solvent recovery techniques. Tetrahydrocannabinol (THC) in cannabis oil reacts with acetic anhydride under reflux to produce THC-O-acetate and acetic acid. The resulting crude product is distilled and subjected to a SALLE with hexane followed by a SALLE with petroleum ether, before being distilled again in order to obtain a refined, THC-O-acetate product.

1 . A process for producing acetylated cannabinol from cannabis oil comprising:
 refluxing cannabis oil with acetic anhydride at a temperature of 120-135° C. to form a crude product;   distilling the crude product at a temperature of 90-125° C. to form a partially refined product;   removing impurities from the partially refined product using a saline water solution wash with hexane;   evaporating hexane from the partially refined product;   removing further impurities from the partially refined product using a saline water solution wash with petroleum ether; and   evaporating petroleum ether from the partially refined product.   
     
     
         2 . The process of  claim 1 , wherein the distilling step removes excess acetic anhydride from the crude product and leaves a precipitate of the partially refined product; and
 the process comprises dissolving the precipitate of the partially refined product in ethanol prior to the saline water solution wash with hexane.   
     
     
         3 . The process of  claim 1 , comprising:
 agitating the cannabis oil and acetic anhydride during the refluxing step;   condensing the cannabis oil and acetic anhydride at a temperature of −5° C. to −10° C. during the refluxing step; and   agitating the crude product during the distilling step;   
       wherein:
 the refluxing is performed under an oxygen-free atmosphere; and 
 the distilling step is performed under a vacuum pressure between 800 and 940 mbar. 
 
     
     
         4 . The process of  claim 1 , comprising preparing saline water for the saline water solution washes with 90-100 g of sodium chloride per 1000 mL of deionized water. 
     
     
         5 . The process of  claim 1 , wherein the saline water solution wash with hexane uses a volume of hexane that is at least half a volume of the saline water solution. 
     
     
         6 . The process of  claim 1 , wherein the saline water solution wash with petroleum ether uses a volume of petroleum ether that is at least half a volume of the saline water solution. 
     
     
         7 . The process of  claim 1 , wherein each removing step comprises:
 agitating the partially refined product during the respective saline water solution wash;   measuring that a bottom phase of a two-phase liquid resulting from the agitation has a pH of 7±0.2;   discarding the bottom phase; and   retaining a top phase of the two-phase liquid.   
     
     
         8 . The process of  claim 7  comprising adding more hexane or petroleum ether to the respective saline water solution wash if the pH of the bottom phase is previously measured to be not equal to 7±0.2. 
     
     
         9 . The process of  claim 7  comprising measuring an optical clarity of the bottom phase to check that the bottom phase is transparent. 
     
     
         10 . The process of  claim 7 , comprising:
 cooling the retained top phase in an environment set to a temperature of −70 to −80° C.; and   discarding impurities that settle during the cooling.   
     
     
         11 . The process of  claim 1 , wherein:
 evaporating the hexane is conducted using a rotary evaporator set at a temperature of 60° C. with a vacuum pressure of 660-940 mbar; and   evaporating the petroleum ether is conducted using the rotary evaporator or another rotary evaporator set at a temperature of 60° C. with a vacuum pressure of 660-940 mbar.   
     
     
         12 . The process of  claim 1 , comprising, after evaporating petroleum ether, heating the partially refined product to a temperature 80° C. for 1 hour to remove traces of petroleum ether and hexane from the partially refined product. 
     
     
         13 . The process of  claim 12 , comprising, after the heating, distilling the partially refined product at a temperature of 200-220° C. to remove compounds other than acetylated cannabinol from the partially refined product. 
     
     
         14 . The process of  claim 13 , wherein distilling the partially refined product is conducted with a short path distillation device, a spinning band distillation device or a wiped film distillation device. 
     
     
         15 . The process of  claim 1 , wherein the cannabis oil is cannabis distillate oil. 
     
     
         16 . The process of  claim 1 , wherein the refluxing step is conducted for 8-10 hours.