WO2007041167A2 - Process for production of delta-9-tetrahydrocannabinol - Google Patents
Process for production of delta-9-tetrahydrocannabinol Download PDFInfo
- Publication number
- WO2007041167A2 WO2007041167A2 PCT/US2006/037709 US2006037709W WO2007041167A2 WO 2007041167 A2 WO2007041167 A2 WO 2007041167A2 US 2006037709 W US2006037709 W US 2006037709W WO 2007041167 A2 WO2007041167 A2 WO 2007041167A2
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- compound
- process according
- substituted
- acyl
- unsubstituted alkyl
- Prior art date
Links
- 0 CC(C(CCC(C)=C1)C1c(c(O*)c(*)c(*)c1*)c1O)=C Chemical compound CC(C(CCC(C)=C1)C1c(c(O*)c(*)c(*)c1*)c1O)=C 0.000 description 3
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/78—Ring systems having three or more relevant rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C37/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring
- C07C37/11—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring by reactions increasing the number of carbon atoms
- C07C37/16—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring by reactions increasing the number of carbon atoms by condensation involving hydroxy groups of phenols or alcohols or the ether or mineral ester group derived therefrom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
- C07C67/333—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton
- C07C67/343—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/16—Systems containing only non-condensed rings with a six-membered ring the ring being unsaturated
Definitions
- the present invention relates to processes for preparation of (-)-trans- delta-9-tetrahydrocannabinol, intermediate compounds thereof, and derivative compounds thereof.
- delta-9-tetrahydrocannabinol delta-9-THC
- delta-9-THC delta-9-tetrahydrocannabinol
- cannabinoids In addition to uses as anaesthetics, spasmolytics, and hypnotics, cannabinoids have been used to combat emesis and nausea induced by cancer chemotherapy, and also in the treatment of glaucoma. In recent times, cannabinoids have achieved a certain notoriety due to their abuse potential. A significant portion of the synthetic effort has been directed toward the preparation of some of the oxygenated human urinary metabolites of delta- 9-THC for use in forensic science as analytical standards for the detection of marijuana use.
- the present invention relates to a process for preparation of a product compound of the formula:
- R 1 is H, substituted or unsubstituted alkyl, carboxylic ester, or acyl
- R 2 is H, OH, protected hydroxyl, substituted or unsubstituted alkyl, alkenyl, alkynyl, acyl, aryl, or heteroaryl;
- R 3 is H, substituted or unsubstituted alkyl, carboxylic ester, or acyl
- R 4 is H, substituted or unsubstituted alkyl, silyl, hetero-substituted or unsubstituted acyl, alkylsulfonyl, arylsulfonyl, alkylphosphoryl, or arylphosphoryl.
- organoaluminum-based Lewis acid catalyst under conditions effective to produce the product compound.
- Another aspect of the present invention relates to a process for preparation of a product compound of the formula: - A -
- R 1 is H, substituted or unsubstituted alkyl, carboxylic ester, or acyl
- R 2 is H, OH, protected hydroxyl, substituted or unsubstituted alkyl, alkenyl, alkynyl, acyl, aryl, or heteroaryl;
- R 3 is H, substituted or unsubstituted alkyl, carboxylic ester, or acyl
- R 4 is H, substituted or unsubstituted alkyl, silyl, hetero-substituted or unsubstituted acyl, alkylsulfonyl, arylsulfonyl, alkylphosphoryl, or arylphosphoryl;
- R 6 is H, substituted or unsubstituted alkyl, silyl, hetero-substituted or unsubstituted acyl, alkylsulfonyl, arylsulfonyl, alkylphosphoryl, or arylphosphoryl.
- the process involves reacting a first starting compound of the formula:
- X H, alkyl, acyl, silyl, aryl, lieteroaryl, sulfonyl, phosphoryl, or phosphinyl, in the presence of a metal triflate catalyst, under conditions effective to form the product compound.
- Yet another aspect of the present invention relates to a process for preparation of a product compound of the formula:
- R 1 is H, substituted or unsubstituted alkyl, carboxylic ester, or acyl
- R 2 is H, OH, protected hydroxyl, substituted or unsubstituted alkyl, alkenyl, alkynyl, acyl, aryl, or heteroaryl;
- R 3 is H, substituted or unsubstituted alkyl, carboxylic ester, or acyl; and R 4 is SO 2 R 5 , wherein R 5 is substituted or unsubstituted alkyl.
- R 4 1 is H, substituted or unsubstituted alkyl, silyl, hetero-substituted or unsubstituted acyl, alkylsulfonyl, arylsulfonyl, alkylphosphoryl, or arylpliosphoryl,
- R 6 is H, substituted or unsubstituted alkyl, silyl, hetero-substituted or unsubstituted acyl, alkylsulfonyl, arylsulfonyl, alkylphosphoryl, or arylphosphoryl, wherein at least one OfR 4 ' and R 6 must be H;
- X H, alkyl, acyl, silyl, aryl, heteroaryl, sulfinyl, sulfonyl, phosphoryl, or phosphinyl, in the presence of a metal triflate catalyst, under conditions effective to form a second intermediate compound of the formula:
- the second intermediate compound is treated with an organoaluminum-based Lewis acid catalyst, under conditions effective to produce a third intermediate compound of the formula:
- the third intermediate compound is reacted with a substituted or unsubstituted alkylsulfonyl halide, alkylsulfonyl anhydride, alkylsulfonyl mixed anhydride, alkylsulfonyl ester, or alkylsulfonic acid, under conditions effective to produce the product compound.
- a substituted or unsubstituted alkylsulfonyl halide, alkylsulfonyl anhydride, alkylsulfonyl mixed anhydride, alkylsulfonyl ester, or alkylsulfonic acid under conditions effective to produce the product compound.
- the present invention also relates to a compound of the formula:
- R 1 is H, substituted or unsubstituted alkyl, carboxylic ester, or acyl
- R 2 is H, OH 5 protected hydroxyl, substituted or unsubstituted alkyl, alkenyl, alkynyl, acyl, aryl, or heteroaryl;
- R 3 is H, substituted or unsubstituted alkyl, carboxylic ester, or acyl
- R 8 , R 9 , and R 10 are the same or different and independently selected from the group consisting of H, substituted or unsubstituted alkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, or halo; and R 8 and R 9 ; R 8 and R 10 ; or R 9 and R 10 ; or R 8 , R 9 , and R 10 can together result in the formation of a cyclic moiety.
- the method of the present invention by the slow addition of a substoichiometric amount of menthadienol to a mixture of olivetol and a metal triflate catalyst in DCM at a temperature above its boiling point, gives vastly improved selectivities for cannabidiol over its unwanted regioisomer over the prior art, and also significantly reduces the transformation of the cannabidiol into cyclized products.
- the cyclization of cannabidiol to delta-9-THC is a notoriously difficult reaction to control and carry out selectively.
- catalysts such as BF 3 OEt 2 , have been used.
- the present invention relates to a process for preparation of a product compound of the formula:
- R 1 is H, substituted or unsubstituted alkyl, carboxylic ester, or acyl
- R 2 is H, OH, protected hydroxyl, substituted or unsubstituted alkyl, alkenyl, alkynyl, acyl, aryl, or heteroaryl;
- R 3 is H, substituted or unsubstituted alkyl, carboxylic ester, or acyl
- R 4 is H, substituted or unsubstituted alkyl, silyl, hetero-substituted or unsubstituted acyl, alkylsulfonyl, arylsulfonyl, alkylphosphoryl, or arylphosphoryl.
- the process involves treating a first intermediate compound of the formula:
- organoaluminum-based Lewis acid catalyst under conditions effective to produce the product compound.
- the organoaluminum-based Lewis acid catalyst used in the method of the present invention can be a trialkyl- or triarylaluminum, dialkyl- or diarylaluminum halide, alkylarylaluminum halide, dialkyl- or alkylaryl- or diarylaluminum alkoxide or aryloxide, dialkyl- or alkylaryl or diarylaluminum thioalkoxide or thioarylate, dialkyl- or alkylaryl or diarylaluminum carboxylate, alkyl- or arylaluminum dihalide, alkyl- or arylaluminum dialkoxide or diaryloxide or alkylaryloxide, alkyl- or aryl aluminum dithioalkoxide or dithioarylate, alkyl- or arylaluminum dicarboxylate, aluminum trialkoxide or triaryloxide or mixed alkylaryloxide, aluminum triacylcarboxylate or mixtures
- organoaluminum-based Lewis acid catalysts include, but are not limited to, ⁇ rimethylaluminum, triethylaluminum, triisopropylaluminum, triisobutylaluminum, trioctylaluminum, tridecylaluminum, diethylaluminum chloride, diisobutylaluminum chloride, diethylaluminum sesquichloride, ethyl aluminum dichloride, methylaluminum dichloride, isobutylaluminum dichloride, diethylaluminum ethoxide, diethylaluminum isopropoxide, diisobutylaluminum methoxide, diisobutylaluminum phenoxide, diphenylaluminum isoproproxide, tetraisobutylalumoxane, methylalumoxane, methylaluminum bis-(2,6-di-t
- the organoaluminum- based Lewis acid catalyst is a C 1 -C 30 alkylaluminum-based or C 6 -C 30 arylaluminum- based substance or mixture.
- the organoaluminum-based Lewis acid catalyst contains one or more oxygenated substituents bonded to the aluminum which modify the physical properties or performance of the catalyst.
- the organoaluminum-based Lewis acid catalyst may be made in situ before use by reaction of a precursor aluminum reagent with a modifying substituent.
- the organoaluminum-based Lewis acid catalysts can be catalysts which provide high selectivity for delta-9-THC at lower levels of catalyst usage and at convenient rates for larger scale preparation. More specifically, the organoaluminum-based Lewis acid catalysts can be catalysts that produce delta-9-THC with very low levels of isomers (e.g., ezs-delta-9-THC, delta-8-THC, and wo-THC), as these are difficult to remove from the product and render it difficult to achieve current standards of pharmaceutical purity.
- the step of treating is carried out with the organoaluminum-based Lewis acid catalyst in an amount from about 0.5 mol% to about 100 mol% with respect to the first intermediate compound.
- the step of treating is carried out with the organoaluminum-based Lewis acid catalyst in an amount from about 5 mol% to about 15 mol% with respect to the first intermediate compound.
- the step of treating can be carried out in an organic solvent, hi one embodiment of the present invention, the solvent is aprotic. Examples of organic solvent include, but are not limited to, hexane, heptane, toluene, xylene, dichloromethane, and mixtures thereof.
- the step of treating can be carried out at a temperature of from about
- the step of treating can be carried out at a temperature of from about -2O 0 C to about 50°C. In yet another embodiment of the present invention, the step of treating can be carried out at a temperature of from about O 0 C to about 30 0 C.
- R 1 is H, substituted or unsubstituted alkyl, carboxylic ester, or acyl
- R 2 is H, OH, protected hydroxyl, substituted or unsubstituted alkyl, alkenyl, alkynyl, acyl, aryl, or heteroaryl;
- R 3 is H, substituted or unsubstituted alkyl, carboxylic ester, or acyl
- R 4 '" is SO 2 R 5 , wherein R 5 is substituted or unsubstituted alkyl.
- the product compound can be reacted with similar arylsulfonyl reagents to produce arylsulfonate compounds.
- the above reaction is carried out with an alkylsulfonyl compound in an amount from about 1 to about 1.5 equivalents with respect to the product compound at atmospheric pressure at a temperature of from about -20 0 C to about 100 0 C depending on the reagent.
- alkylsulfonyl chloride is used, for example, the reaction is typically carried out at a temperature of from about -10 0 C to about 20 0 C.
- the product compound can be a totally synthetic substance or a naturally derived substance.
- the process of the present invention further involves carrying out a method selected from chromatography, countercurrent extraction, and distillation on the second product compound under conditions effective to produce a purified second product compound.
- the process of the present invention further involves crystallizing the second product compound under conditions effective to produce a purified second product compound.
- the purified second product compound can be hydrolyzed under conditions effective to produce the purified product compound in a desired isomer form.
- the step of hydrolyzing is carried out in the presence of an organic or inorganic base in a solvent.
- bases include, but are not limited to, sodium hydroxide, potassium t-butoxide, and mixtures thereof.
- solvent include, but are not limited to, methanol, ethanol, isopropanol, t-butanol, acetonitrile, and mixtures thereof.
- the second product compound is of the formula:
- R 8 , R 9 , and R 10 are the same or different and independently selected from the group consisting of H, substituted or unsubstituted alkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, or halo;
- R 8 and R 9 ; R 8 and R 10 ; or R 9 and R 10 ; or R 8 , R 9 , and R 1 O can together result in the formation of a cyclic moiety.
- Alkyl is defined herein as C 1 -C n , wherein the carbon chains may be straight, branched, or containing or comprising rings.
- Substituted alkyl is defined as C 1X- C n X as described above, except that the carbons may bear one or more substituents X, such as functional groups containing oxygen, nitrogen, sulfur, halogen or aromatic or heteroaromatic rings.
- Aryl is defined as C 6 -C n aromatic rings or multiple rings.
- “Substituted aryl” is defined as C 6 -C n aromatic rings or multiple rings bearing substituents on one or more of these rings which may be functional groups of carbon, oxygen, nitrogen, sulfur or halogen.
- Heteroaryl is defined as aromatic rings containing one or more heteroatom within the ring or rings.
- Substituted heteroaryl is defined as heteroaryl containing one or more substituents on one or more ring which may be functional groups of carbon, oxygen, nitrogen, sulfur or halogen.
- Halo is defined as chlorine, bromine, iodine or fluorine.
- R 8 , R 9 , and Ri 0 may contain chiral centers or define a chiral center on the carbon bearing them.
- the second product compound is a straight chain alkylsulfonate selected from methanesulfonate, ethanesulfonate, propanesulfonate, butanesulfonate, pentanesulfonate, hexanesulfonate, heptanesulfonate, octanesulfonate, nonanesulfonate, decanesulfonate, undecanesulfonate, dodecanesulfonate, tridecanesulfonate, tetradecanesulfonate, pentadecanesulfonate, hexadecanesulfonate, heptadecanesulfonate, octadecanesulfonate, nonadecanesulfonate, and icosanesulfonate.
- the second product compound is a branched chain alkylsulfonate selected from cyclopropylsulfonate, isopropylsulfonate, isobutylsulfonate, fert-octylsulfonate, adamantly sulfonate, and 10-camphorsulfonate.
- the second product compound is a substituted alkylsulfonate selected from chloromethylsulfonate, 2- chloroethylsulfonate j trifluoromethylsulfonate, trifluorethylsulfonate, perfluoroethylsulfonate, perfluorobutylsulfonate, perfluorooctanesulfonate, 2- aminoethylsulfonate, 2-dimethylaminoethylsulfonate, 2-phthalimidoethylsulfonate, 2- morpholinoetliylsulfonate, 3 -morpholinopropylsulfonate, 4-morpholinobutylsulfonate, 2-N-piperidinylethylsulfonate, 3-N-piperidylpropylsulfonate, 2- pyrrolidinylmethylsulfonate
- the second product compound can have the following formula, where the camphorsulfonate group is in the R configuration:
- the second product compound is a diastereomeric mixture of the following two formulae, where the camphorsulfonate group is in the S and R configurations, respectively:
- the second product compound is an aryl or heteroaryl substituted alkylsulfonate selected from benzylsulfonate, 2-nitrobenzylsulfonate, 3-nitrobenzylsulfonate, 4- nitrobenzylsulfonate, 2-chlorobenzylsulfonate, 3-chlorobenzylsulfonate, 4- chlorobenzylsulfonate, 2-trifluoromethybenzylsulfonate, 3- trifluoromethylbenzylsulfonate, 4-trifluoromethylbenzylsulfonate, 3,5- dichlorobenzylsulfonate, 3,5-di-trifluoromethylbenzylsulfonate, 4- methylbenzylsulfonate, 4-t-butylbenzylsulfonate, 1-napthylethylsulfonate, 2- pyridylmethylsulfonate, 3-
- the process of the present invention further involves reacting a second intermediate compound of the formula:
- R 6 is H, substituted or unsubstituted alkyl, silyl, hetero-substituted or unsubstituted acyl, alkylsulfonyl, arylsulfonyl, alkylphosphoryl, or arylphosphoryl; with a second compound of the formula:
- X H, alkyl, acyl, silyl, aryl, heteroaryl, sulfinyl, sulfonyl, phosphoryl, or phosphinyl, in the presence of a metal triflate catalyst, under conditions effective to form the first intermediate compound.
- the step of reacting is carried out under conditions effective to achieve preferential formation of the first intermediate compound over undesired stereochemical and regiochemical isomers as well as other impurities.
- R 1 is H or COOR 7
- R 2 is W-C 5 H 11
- R 3 is H or COOR 7 , where R 7 is C 1 -C 20 alkyl.
- R 1 is COOR 7 , where R 7 is ethyl
- R 2 is W-C 5 H 11
- R 3 is H or COOR 7 , where R 7 is C 1 -C 2O alkyl
- R 4 H
- X H.
- R 2 Az-C 5 H 11
- X H.
- the above reaction is carried out with the second intermediate compound in an amount of from about 1 to 1.2 equivalents with respect to the second compound.
- the metal triflate catalyst can be a transition metal triflate or lanthanide triflate. Examples of transition metal triflate include, but are not limited to, zinc triflate, ytterbium triflate, yttrium triflate, and scandium triflate. Specifically, the transition metal triflate is zinc triflate or scandium triflate.
- the step of reacting is carried out with the metal triflate catalyst in an amount from about 0.5 mol% to about 100 mol% with respect to the second intermediate compound. In yet another embodiment of the present invention, the step of reacting is carried out with the metal triflate catalyst in an amount from about 0.5 mol% to about 10 mol% with respect to the second intermediate compound.
- the step of reacting is carried out in an organic solvent.
- organic solvent include, but are not limited to, a hydrocarbon, aromatic hydrocarbon, halogenated hydrocarbon, ether, ester, amide, nitrile, carbonate, alcohol, carbon dioxide, and mixtures thereof.
- the organic solvent is dichloromethane.
- the step of reacting is carried out at a temperature of from about -2O 0 C to about 15O 0 C.
- the step of reacting can be carried out under pressure at a temperature above the normal atmospheric boiling point of the organic solvent or where temperatures are above boiling point and pressure is above atmosphere.
- the step of reacting is carried out with a less than about one equivalent of the second compound to the second intermediate compound.
- Ethyl olivetolate (25 g, 99 mmol) was dissolved in dichloromethane (250 mL) and MgSO 4 (25 g, 1 wt) and Sc(OTf) 3 (4.88 g, 9.9 mmol, 10 mol%) were added sequentially.
- the reaction mixture was quenched with aqueous citric acid (129.6 g citric acid, 8.3 equiv, as a 30% solution in water). The addition was exothermic. Heptane (310 mL, 10 vol) was added to the mixture and the product extracted into the heptane phase. A second extraction using heptane (150 mL, ca. 5 vol) was then performed and HPLC analysis of the aqueous fractions indicated the absence of the cannabidiol. The combined organics were dried by azeotropic distillation of the water and concentrated to ca. 250 mL and then cooled to -16 to -17°C, and seeded with solid cannabidiol when the temperature reached -1.5 0 C.
- Example 5 Preparation of (-)-trans-delta-9- ⁇ HC [0049] Ir ⁇ 5-delta-9-THC 3-nitrobenzenesulfonate (16.5 g) was dissolved in acetonitrile (330 mL, 20 vol) and 0.5 M NaOH (165 mL, 10 vol) was added. The mixture was heated to reflux and, after ca. 2 h, HPLC analysis indicated that the reaction was complete. After cooling, water (500 mL, 30 vol) was added followed by heptane (165 mL, 10 vol). The phases were mixed and the heptane layer was collected.
- the aqueous phase was extracted again with heptane (165 mL, 10 vol) and the organic extracts were combined, washed with water (165 mL, 10 vol), dried over Na 2 SO 4 , filtered, and concentrated to a dark brown-purple oil.
- the oil was reconstituted with EtOH and restripped to give the product as a light brown oil (10.79 g), containing ca. 6% EtOH by proton NMR analysis. HPLC analysis indicated a purity of 99.66% AUC.
- the nonvolatile fraction (14.7 kg of thiophenyl ether) was dissolved in glacial acetic acid (26.0 L) and stirred while 35% hydrogen peroxide (6.0 kg) added over 6.5 hours.
- the reaction temperature was maintained at 10-20 0 C.
- the reaction was allowed to warm to room temperature overnight, then transferred into a mixture of warm water (89 L, 40-45 0 C) and MTBE (34 L).
- the organic phase was washed aqueous 5% sodium bicarbonate (4 washes, 18 L each) at 40-45 0 C, to achieve a final pH of ca. 8 and a negative starch-iodine test.
- Example 8 Preparation of Ethyl Cannabidiolate [0055] To a stirred solution of ethyl olivetolate (40.1 g, 155 mmol) in dichloromethane (360 mL) was added anhydrous magnesium sulfate (10.4 g) and scandium triflate (3.93 g, 8 mmol). The mixture was cooled to 10 0 C. To this slurry was added a cold solution of (+)-menthadienol (25.1 g, 155 mmol) in dichloromethane (160 mL) over three minutes, followed by a dichloromethane rinse (120 mL). A slight exotherm was observed.
- Example 9 Preparation of Cannabidiol
- Crude ethyl cannabidiolate 58.6 g, ca. 90% pure by HPLC
- methanol 390 mL
- Aqueous sodium hydroxide solution 80.8 g of NaOH in 390 mL of water
- the hydroxide solution was transferred under nitrogen pressure, through a steel cannula to the hot ethyl cannabidiolate/methanol solution over 20 minutes while maintaining the reaction at 7O 0 C.
- the slowly stirred heptane solution was cooled to 10 0 C, seeded with cannabidiol crystals and stirred slowly at 10 0 C for three hours to develop a crop of crystals.
- the slurry was stored overnight at -5°C.
- the solid product was collected by filtration on cold sintered glass and the reactor and cake rinsed with cold heptane (150 mL). The solids were dried under nitrogen stream for two hours then under reduced pressure at 2O 0 C for 15 hours to afford 21 g (44% yield) of solid cannabidiol.
- the reaction was quenched by addition of water (250 mL), stirred 30 minutes, combined with a slurry of celite in dichloromethane (10.0 g in 70 mL dichloromethane) and then clarified.
- the reactor and filter cake were rinsed with dichloromethane (50 mL) and the combined filtrates distilled under reduced pressure (25°C pot temperature, 22 inches of vacuum) to about 50 mL volume.
- Toluene (106 mL) was added and the solvents again removed under reduced pressure. More toluene (106 mL) was added and removed under reduced pressure and then the dichloromethane-free residue was reconstituted in toluene (100 mL).
- the toluene layer was concentrated under reduced pressure to about 100 mL and additional toluene (100 mL) was added. This drying sequence was repeated and then the solvent was replaced with isopropanol (200 mL). The isopropanol was concentrated under reduced pressure and the residue was suspended in isopropanol (200 mL). The slurry was warmed to 40 0 C at which point the solids dissolved. The stirred solution was cooled to 20 0 C over 4 hours during which the product crystallized.
- Example 13 Preparation of Delta-9-Tetrahydrocannabinol in Sesame Oil
- a stock solution of delta-9 THC in ethanol (6.90 g of 0.109 mg/mL tetrahydrocannabinol concentration) was mixed with Croda high purity sesame oil (29.25 g) from Croda, Inc. (Edison, NJ).
- the resulting solution was warmed to 3O 0 C, and sparged with filtered argon for 24 hours to afford ca. 30 g of 2.5 % delta-9- tetrahydrocannabinol in sesame oil.
- 1 H NMR 500 MHz (CDCl 3 ) showed no residual ethanol.
Priority Applications (7)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP06804207A EP1928853A4 (en) | 2005-09-29 | 2006-09-28 | PROCESS FOR THE PRODUCTION OF DELTA-9-TETRAHYDROCANNABINOL |
NZ567029A NZ567029A (en) | 2005-09-29 | 2006-09-28 | Process for production of delta-9- tetrahydrocannabinol |
AU2006297300A AU2006297300B2 (en) | 2005-09-29 | 2006-09-28 | Process for production of delta-9-tetrahydrocannabinol |
JP2008533571A JP2009510078A (ja) | 2005-09-29 | 2006-09-28 | Δ−9−テトラヒドロカンナビノールの生成法 |
CA002623723A CA2623723A1 (en) | 2005-09-29 | 2006-09-28 | Process for production of delta-9-tetrahydrocannabinol |
NZ594077A NZ594077A (en) | 2005-09-29 | 2006-09-28 | Process for production of delta-9-tetrahydrocannabinol |
IL190388A IL190388A0 (en) | 2005-09-29 | 2008-03-24 | Process for production of delta-9-tetrahydrocannabinol |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US72203105P | 2005-09-29 | 2005-09-29 | |
US60/722,031 | 2005-09-29 |
Publications (2)
Publication Number | Publication Date |
---|---|
WO2007041167A2 true WO2007041167A2 (en) | 2007-04-12 |
WO2007041167A3 WO2007041167A3 (en) | 2007-11-22 |
Family
ID=37906689
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US2006/037709 WO2007041167A2 (en) | 2005-09-29 | 2006-09-28 | Process for production of delta-9-tetrahydrocannabinol |
Country Status (11)
Cited By (17)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2008099183A1 (en) * | 2007-02-14 | 2008-08-21 | Resolution Chemicals Limited | Delta 9 tetrahydrocannabinol derivatives |
WO2009073633A1 (en) * | 2007-11-30 | 2009-06-11 | Alltranz Inc. | Prodrugs of tetrahydrocannabinol, compositions comprising prodrugs of tetrahydrocannabinol and methods of using the same |
WO2009099868A1 (en) * | 2008-02-06 | 2009-08-13 | Mallinckrodt Inc. | Process for the preparation of (-) -delta 9-tetrahydrocannabinol |
US8530679B2 (en) | 2007-02-20 | 2013-09-10 | Resolution Chemicals Limited | Delta 9—tetrahydrocannabinol processing |
EP3253727A4 (en) * | 2015-02-05 | 2018-08-08 | Colorado Can LLC | Purified cbd and cbda, and methods, compositions and products employing cbd or cbda |
WO2019030158A1 (en) | 2017-08-07 | 2019-02-14 | Enantia, S.L. | CO-CRYSTAL OF 2 - [(1R, 6R) -6-ISOPROPENYL-3-METHYLCYCLOHEX-2-EN-1-YL] -5-PENTYLBENZENE-1,3-DIOL |
WO2019033168A1 (en) * | 2017-08-16 | 2019-02-21 | The University Of Sydney | SYNTHESIS OF PHYTOCANNABINOIDS COMPRISING A DECARBOXYLATION STAGE |
EP3539637A1 (en) * | 2018-03-13 | 2019-09-18 | CLS Labs, Inc. | Cannabidiol extraction and conversion process |
WO2020089424A1 (en) | 2018-10-31 | 2020-05-07 | Enantia, S.L. | Solid compositions of cocrystals of cannabinoids |
WO2020198876A1 (en) * | 2019-04-05 | 2020-10-08 | Rapid Dose Therapeutics Corp. | Apparatus for and method of converting cbd and/or cbd derivatives to at least one other type of cannabinoid and/or cannabinoid derivative such as thc |
WO2020232526A1 (en) * | 2019-05-17 | 2020-11-26 | Nextleaf Solutions Ltd | Method for acetylation of cannabinoids |
WO2021046630A1 (en) * | 2019-09-15 | 2021-03-18 | Nextleaf Solutions Ltd | Acetylation of cannabinoids using sulfuric acid catalyst |
US20210106929A1 (en) * | 2018-08-10 | 2021-04-15 | Natural Extraction Systems, LLC | Methods to purify cannabinoids |
WO2021181420A1 (en) | 2020-03-12 | 2021-09-16 | Council Of Scientific And Industrial Research An Indian Registered Body Incorporated Under The Regn. Of Soc. Act (Act Xxi Of 1860) | Process for the synthesis of cannabidiol and intermediates thereof |
WO2021198692A1 (en) | 2020-03-31 | 2021-10-07 | Phytotherapeutix Ltd | Terpenophenolic compounds and their use |
EP3983395A4 (en) * | 2019-06-11 | 2023-10-18 | Canopy Growth Corporation | IMPROVED PROCESSES FOR CONVERTING CANNABIDIOL TO DELTA 8-TETRAHYDROCANNABINOL |
WO2024028516A1 (en) | 2022-08-05 | 2024-02-08 | Salud & Semillas, S.L. | CANNABINOID SYNTHESIS STARTING OUT FROM OLIVETOL AND TERPENE IN DICHLOROMETHANE WITH FeCl3 * 6H2O AS CATALYST |
Families Citing this family (55)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US8980940B2 (en) | 2006-11-10 | 2015-03-17 | Johnson Matthey Public Limited Company | Stable cannabinoid compositions and methods for making and storing them |
US8039509B2 (en) | 2006-11-10 | 2011-10-18 | Johnson Matthey Public Limited Company | Composition comprising (−)-Δ9-trans-tetrahydrocannabinol |
GB0807915D0 (en) * | 2008-05-01 | 2008-06-04 | Resolution Chemicals Ltd | Production of delta 9 tetrahydrocannabinol |
US8445034B1 (en) | 2010-11-02 | 2013-05-21 | Albert L Coles, Jr. | Systems and methods for producing organic cannabis tincture |
EP2842933B1 (de) * | 2013-09-03 | 2015-07-29 | Symrise AG | Mischungen cannabinoider Verbindungen, deren Herstellung und Verwendung |
US10821240B2 (en) | 2014-02-11 | 2020-11-03 | Vapor Cartridge Technology Llc | Methods and drug delivery devices using cannabis |
US9380813B2 (en) | 2014-02-11 | 2016-07-05 | Timothy McCullough | Drug delivery system and method |
US9220294B2 (en) | 2014-02-11 | 2015-12-29 | Timothy McCullough | Methods and devices using cannabis vapors |
US10045540B2 (en) | 2014-04-01 | 2018-08-14 | Fayetteville State University | Pest control composition |
CA2950424C (en) * | 2014-05-29 | 2023-03-14 | Insys Pharma, Inc. | Stable cannabinoid formulations |
GB2531281A (en) | 2014-10-14 | 2016-04-20 | Gw Pharma Ltd | Use of cannabidiol in the treatment of intractable epilepsy |
EP3061450A1 (de) | 2015-02-26 | 2016-08-31 | Symrise AG | Mischungen cannabinoider Verbindungen, deren Herstellung und Verwendung |
US10059683B2 (en) | 2015-07-10 | 2018-08-28 | Noramco, Inc. | Process for the production of cannabidiol and delta-9-tetrahydrocannabinol |
PT3455213T (pt) * | 2016-05-13 | 2022-03-01 | Symrise Ag | Método para purificar compostos canabinoides através de cromatografia em leito móvel simulado |
US10399920B2 (en) | 2016-06-01 | 2019-09-03 | S&B Pharma, Inc. | Crystalline form of cannabidiol |
US10239808B1 (en) | 2016-12-07 | 2019-03-26 | Canopy Holdings, LLC | Cannabis extracts |
CN106632214B (zh) * | 2016-12-28 | 2019-01-25 | 西北大学 | 一种大麻酚类化合物的合成方法 |
US10702495B2 (en) | 2017-02-20 | 2020-07-07 | Nexien Biopharma, Inc. | Method and compositions for treating dystrophies and myotonia |
ES2909350T3 (es) * | 2017-06-20 | 2022-05-06 | Yissum Res Dev Co Of Hebrew Univ Jerusalem Ltd | Composiciones de ésteres de ácido cannabidiólico y usos de las mismas |
US10640482B2 (en) | 2017-07-21 | 2020-05-05 | University Of South Florida | Synthesis of cannabinoids |
US10272360B2 (en) | 2017-08-05 | 2019-04-30 | Priya Naturals, Inc. | Phytochemical extraction system and methods to extract phytochemicals from plants including plants of the family Cannabaceae sensu stricto |
CN111372907A (zh) * | 2017-09-01 | 2020-07-03 | 普优峰全球股份有限公司 | 合成大麻二酚组合物和用于制备其的方法 |
EP3745884A1 (en) | 2018-01-31 | 2020-12-09 | Canopy Holdings, Llc | Hemp powder |
US11192870B2 (en) | 2018-03-07 | 2021-12-07 | Socati Technologies—Oregon, Llc | Continuous isolation of cannabidiol and conversion of cannabidiol to delta 8-tetrahydrocannabinol and delta 9-tetrahydrocannabinol |
US11851415B2 (en) | 2018-03-07 | 2023-12-26 | Cleen Technology Inc. | Continuous isolation of cannabidiol and cannabinoids and conversion of cannabidiol to delta 8-tetrahydrocannabinol and delta 9-tetrahydrocannabinol |
CA3073093A1 (en) | 2018-08-03 | 2020-02-06 | Biomass Oil Separation Solutions, Llc | Processes and apparatus for extraction of substances and enriched extracts from plant material |
WO2020031179A1 (en) | 2018-08-06 | 2020-02-13 | Beetlebung Pharma Ltd. | Methods for synthesis of cannabinoid compounds |
CA3111788A1 (en) | 2018-09-05 | 2020-03-12 | Purisys Llc | Cannabidiol compositions having modified cannabinoid profiles |
US11040932B2 (en) | 2018-10-10 | 2021-06-22 | Treehouse Biotech, Inc. | Synthesis of cannabigerol |
CN109734554B (zh) * | 2019-02-25 | 2021-11-23 | 江苏暨明医药科技有限公司 | 一种反式-薄荷基-2,8-二烯-1-醇的合成工艺 |
EP3958884A4 (en) | 2019-04-23 | 2022-12-21 | Soma Oil LLC | SYSTEMS AND METHODS FOR CANNABIS PROCESSING |
CN111943813B (zh) * | 2019-05-17 | 2023-04-14 | 上海特化医药科技有限公司 | 大麻二酚类化合物的制备方法 |
SG11202112677WA (en) * | 2019-05-23 | 2021-12-30 | Kare Chemical Tech Inc | Catalytic cannabinoid processes and precursors |
EP3750528A1 (en) | 2019-06-11 | 2020-12-16 | Nexien Biopharma, Inc. | Compositions for treating dystrophies and myotonia |
US20220220090A1 (en) * | 2019-06-11 | 2022-07-14 | Canopy Growth Corporation | Improved methods for converting cannabidiol into delta9-tetrahydrocannabinol under neat or aprotic reaction conditions |
WO2020248060A1 (en) * | 2019-06-11 | 2020-12-17 | Canopy Growth Corporation | Improved methods for converting cannabidiol into delta9-tetrahydrocannabinol under protic reaction conditions |
US11925907B2 (en) | 2019-07-22 | 2024-03-12 | Canopy Growth Corporation | Continuous crystallization of cannabinoids in a stirred-tank reactor |
US10799546B1 (en) | 2019-07-26 | 2020-10-13 | Biomass Oil Separation Solutions, Llc | Modular, integrated process and apparatus for extracting, refining and remediating active substances from plant material |
MX2022003189A (es) | 2019-09-16 | 2022-06-08 | Vapor Cartridge Tech Llc | Sistema de administración de fármacos con sustratos apilables. |
US11542243B1 (en) * | 2019-09-26 | 2023-01-03 | FusionFarms, LLC | Method of converting delta9-THC to delta10-THC and the purification of the delta10-THC by crystallization |
EP4069215A4 (en) | 2019-12-06 | 2024-01-17 | JLABS Beauty LLC | TOPICAL COMPOSITIONS CONTAINING ROSE OIL AND CANNABIDIOL AND METHODS OF PREPARING AND USING THE SAME |
EP4088723A4 (en) * | 2020-01-08 | 2024-02-21 | Chengdu Baiyu Pharmaceutical Co Ltd | CANNABIDIOL DERIVATIVE, METHOD FOR THE PRODUCTION THEREOF AND MEDICAL USE THEREOF |
CN113087743B (zh) * | 2020-01-08 | 2023-04-28 | 成都百裕制药股份有限公司 | 四氢大麻酚衍生物及其制备方法和在医药上的应用 |
US11767306B2 (en) * | 2020-01-17 | 2023-09-26 | Cannacraft, Inc | Methods for converting CBD to tetrahydrocannabinols |
US10981849B1 (en) * | 2020-02-20 | 2021-04-20 | Sci Pharmtech Inc. | Method for preparing cannabinoids |
ES2936274T3 (es) | 2020-02-21 | 2023-03-15 | Sci Pharmtech Inc | Método sin disolvente para preparar cannabinoides |
GB202002754D0 (en) | 2020-02-27 | 2020-04-15 | Gw Res Ltd | Methods of treating tuberous sclerosis complex with cannabidiol and everolimus |
US11786838B2 (en) | 2020-03-23 | 2023-10-17 | Cannacraft, Inc. | Methods for removing pesticides from Cannabis products |
CA3179442A1 (en) | 2020-05-22 | 2021-11-25 | Brian Warrington | Compositions for treating acne and dermatological conditions |
CN113896616A (zh) * | 2020-07-06 | 2022-01-07 | 复旦大学 | 一种大麻二酚的制备方法 |
CN112094257B (zh) * | 2020-08-19 | 2023-08-22 | 公安部禁毒情报技术中心 | 一种△-9四氢大麻酚的制备方法 |
CN114644547A (zh) * | 2020-12-21 | 2022-06-21 | 云南汉盟制药有限公司 | 一种大麻二酚和/或次大麻二酚的制备方法 |
CN115504864A (zh) * | 2021-06-07 | 2022-12-23 | 南通新世元生物科技有限公司 | 从工业大麻中获取高纯度大麻二酚的方法 |
CN113979836B (zh) * | 2021-10-13 | 2023-05-30 | 上海应用技术大学 | 一种4-异丙烯基-1-甲基-2-环己烯-1-醇的制备方法 |
CN115583933B (zh) * | 2022-10-31 | 2024-02-06 | 暨明医药科技(苏州)有限公司 | 一种高纯度四氢大麻素同系物的制备方法 |
Family Cites Families (86)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2509387A (en) * | 1950-05-30 | Dibenzopyran marihuana-like | ||
US2304669A (en) * | 1940-08-16 | 1942-12-08 | Adams Roger | Isolation of cannabidiol |
GB558418A (en) | 1940-08-16 | 1944-01-05 | Roger Adams | Process for securing pharmacologically useful products from cannabidiol |
US2419934A (en) * | 1941-07-09 | 1947-05-06 | Adams Roger | Optically active tetrahydrodibenzopyrans having marihuana activity and process for making same |
US2419935A (en) * | 1941-07-09 | 1947-05-06 | Adams Roger | Marihuana active compounds |
US2419936A (en) * | 1942-04-29 | 1947-05-06 | Adams Roger | Preparation of compounds with marihuana activity |
US3636058A (en) * | 1966-03-25 | 1972-01-18 | Hoffmann La Roche | 7 10 - dihydro - 3 - alkyl - 6h - dibenzo(b d) pyran-6 9(8h)-diones and 5-hydroxy-7-alkyl-4-chromanones |
US3507885A (en) * | 1966-03-25 | 1970-04-21 | Hoffmann La Roche | 3-alkyl-6h-dibenzo(b,d)pyrans |
CH473075A (de) * | 1966-11-04 | 1969-05-31 | Theodor Dr Petrzilka | Verfahren zur Herstellung von in 2-Stellung substituierten Resorcinderivaten |
US3920705A (en) * | 1967-05-19 | 1975-11-18 | Theodore Petrzilka | 6a,10a-trans-6a,10,10a-tetrahydrodibenzo(b,d)-pyrans |
US3833616A (en) * | 1968-09-16 | 1974-09-03 | T Petrzilka | 6a,10a-trans-6a,7,8,10a-tetrahydrodibenzo(b,d)-pyrans |
US3919322A (en) * | 1969-01-22 | 1975-11-11 | Hoffmann La Roche | 3-Substituted -5-alkyl-2-cyclohexen-1-ones |
US3734930A (en) * | 1971-09-22 | 1973-05-22 | R Razdan | Direct synthesis of ({31 )-trans-{66 {11 tetrahydrocannabinol from olivetol and ({30 )-trans-{66 {11 -carene oxide |
US4278603A (en) * | 1973-11-05 | 1981-07-14 | Eli Lilly And Company | Novel polymorphic crystalline form of dibenzopyranone |
US4025516A (en) * | 1975-06-23 | 1977-05-24 | The John C. Sheehan Institute For Research, Inc. | Process for the preparation of (-)-6a,10a-trans-6a,7,8,10a-tetrahydrodibenzo[b,d]-pyrans |
US4116979A (en) * | 1975-06-23 | 1978-09-26 | Sheehan Institute For Research, Inc. | Process for the preparation of (-)-6a,10a-trans-6a,7,8,10a-tetrahydrodibenzo[b,d]-pyrans |
IL48824A (en) * | 1976-01-12 | 1980-05-30 | Yissum Res Dev Co | Pharmaceutical compositions containing (3s,js) tetrahydrocanabinol derivatives and some novel compounds of this type |
PT66744B (en) * | 1976-07-06 | 1978-11-27 | Lilly Co Eli | Process for preparing cis-hexahydrodibenzopyranones |
US4054582A (en) * | 1976-07-06 | 1977-10-18 | Eli Lilly And Company | Process for converting cis-hexahydrodibenzo[b,d]pyran-9-ones to trans-hexahydrodibenzo[b,d]-pyran-9-ones |
CA1096390A (en) * | 1976-07-06 | 1981-02-24 | Edward R. Lavagnino | PROCESS FOR PREPARING DL-CIS-1-HYDROXY-3-SUBSTITUTED- 6,6-DIMETHYL-6,6.alpha.,7,8,10,10.alpha.-HEXAHYDRO-9H- DIBENZO(B,D,)PYRAN-9-ONES |
US4102902A (en) | 1976-11-10 | 1978-07-25 | Eli Lilly And Company | Stereoselective preparation of hexahydro dibenzopyranones and intermediates therefor |
US4075230A (en) * | 1976-11-10 | 1978-02-21 | Eli Lilly And Company | Preparation of optically active trans-hexahydrodibenzopyranones |
US4171315A (en) * | 1978-03-31 | 1979-10-16 | Eli Lilly And Company | Preparation of cis-hexahydrodibenzopyranones |
US4202902A (en) * | 1979-03-05 | 1980-05-13 | Shell Oil Company | Lipogenesis control by cyclopropane-carboxylic acids, esters and amides |
CH646933A5 (fr) * | 1981-05-04 | 1984-12-28 | Firmenich & Cie | Procede pour la preparation de (+)-p-mentha-2,8-diene-1-ol. |
US4381399A (en) * | 1981-12-21 | 1983-04-26 | Aerojet-General Corporation | Purification of tetrahydrodibenzo[b,d]pyrans from crude synthetic mixtures |
IL80411A (en) * | 1986-10-24 | 1991-08-16 | Raphael Mechoulam | Preparation of dibenzopyranol derivatives and pharmaceutical compositions containing them |
US4933363A (en) * | 1988-08-16 | 1990-06-12 | Elsohly Mahmoud A | Method for effecting systemic delivery of delta-9-tetrahydrocannabinol |
US5521215A (en) | 1989-11-07 | 1996-05-28 | Ramot University Authority For Applied Research And Industrial Development Ltd. | NMDA-blocking pharmaceuticals |
IL92238A (en) | 1989-11-07 | 1995-07-31 | Yissum Res Dev Co | ADMN blocking product containing tetrahydrocannabinol history, several new tetrahydrocannabinol histories and process for their preparation |
DE4100441A1 (de) * | 1991-01-09 | 1992-07-16 | Mack Chem Pharm | Verfahren zur herstellung von 6,12-dihydro-6-hydroxy-cannabidiol und dessen verwendung zur herstellung von trans-delta-9-tetrahydrocannabinol |
US5635530A (en) * | 1991-09-12 | 1997-06-03 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | (3S,4S)-delta-6-tetrahydrocannabinol-7-oic acids and derivatives thereof, processors for their preparation and pharmaceutical compositions containing them |
US5538993A (en) * | 1991-09-12 | 1996-07-23 | Yissum Research Development Company | Certain tetrahydrocannabinol-7-oic acid derivatives |
US5292899A (en) * | 1991-11-27 | 1994-03-08 | Synthetic Technology Corporation | Synthesis of 11-nor-Δ-9-tetrahydrocannabinol-9-carboxylic acid glucuronide |
IL102082A (en) * | 1992-06-02 | 1997-07-13 | Yissum Res Dev Co | Antiemetic composition containing a cannabinol derivative |
US5338753A (en) * | 1992-07-14 | 1994-08-16 | Sumner H. Burstein | (3R,4R)-Δ6 -tetrahydrocannabinol-7-oic acids useful as antiinflammatory agents and analgesics |
US5342971A (en) * | 1992-12-29 | 1994-08-30 | The Australian National University | Process for the preparation of dibenzo[b,d]pyrans |
US5389375A (en) * | 1993-05-21 | 1995-02-14 | University Of Mississippi | Stable suppository formulations effecting bioavailability of Δ9 -thc |
US5440052A (en) * | 1993-08-06 | 1995-08-08 | University Of Connecticut | Compositions useful as a cannabinoid receptor probe |
JPH07196565A (ja) * | 1993-12-28 | 1995-08-01 | Idemitsu Petrochem Co Ltd | 4−アルキル−2−フルオロシクロヘキサノールとその製造方法及びその光学分割方法 |
IL115245A (en) * | 1995-09-11 | 2002-12-01 | Yissum Res Dev Co | Tumor necrosis factor inhibiting pharmaceuticals |
US6328992B1 (en) | 1997-03-03 | 2001-12-11 | Lawrence L. Brooke | Cannabinoid patch and method for cannabis transdermal delivery |
US6148261A (en) * | 1997-06-20 | 2000-11-14 | American Calcar, Inc. | Personal communication system to send and receive voice data positioning information |
US6162829A (en) * | 1997-10-17 | 2000-12-19 | Atlantic Pharmaceuticals, Inc. | (3R,4R)-Δ8 -tetrahydrocannabinol-11-oic acids useful as antiinflammatory agents and analgesics |
EP1071419B1 (en) * | 1998-04-21 | 2007-07-25 | THE UNITED STATES GOVERNMENT as represented by THE DEPARTMENT OF HEALTH AND HUMAN SERVICES | Cannabinoids as antioxidants and neuroprotectants |
AU6291999A (en) * | 1998-10-05 | 2000-04-26 | B.F. Goodrich Company, The | Catalyst and methods for polymerizing cycloolefins |
US6730519B2 (en) * | 1998-10-26 | 2004-05-04 | The University Of Mississippi | Method of preparing delta-9-tetrahydrocannabinol |
US6008383A (en) * | 1998-10-26 | 1999-12-28 | University Of Mississippi | Method of preparing delta-9-tetrahydrocannabinol esters |
US6566560B2 (en) * | 1999-03-22 | 2003-05-20 | Immugen Pharmaceuticals, Inc. | Resorcinolic compounds |
EP1189603A2 (en) * | 1999-03-22 | 2002-03-27 | Immugen Pharmaceuticals, Inc. | Treatment of immune diseases like hiv disease and neoplastic disorders |
US6949582B1 (en) * | 1999-05-27 | 2005-09-27 | Wallace Walter H | Method of relieving analgesia and reducing inflamation using a cannabinoid delivery topical liniment |
FR2795731B1 (fr) * | 1999-07-02 | 2001-09-07 | Warner Lambert Co | PROCEDE DE PREPARATION DE [1,4] DIAZEPINO [6,7,1-hi] INDOL-4-ONES SUBSTITUEES |
WO2001003690A1 (en) * | 1999-07-12 | 2001-01-18 | Virginia Commonwealth University | Novel vasodilator cannabinoid analogs |
MXPA02001804A (es) | 1999-08-20 | 2004-09-06 | Unimed Pharmaceuticals Inc | Composicion para inhalacion que comprende delta-9-tetrahidrocanabinol en un solvente semi-acuoso. |
CA2404669A1 (en) * | 2000-03-27 | 2001-10-04 | Akiko Asakawa | Condensed pyrazole derivatives, process for producing the same and use thereof |
US6448288B1 (en) * | 2000-05-17 | 2002-09-10 | University Of Massachusetts | Cannabinoid drugs |
US6974835B2 (en) * | 2000-05-17 | 2005-12-13 | Indevus Pharmaceuticals, Inc. | Methods for decreasing cell proliferation based on (3r,4r)-Δ8-tetrahydrocannabinol-11-oic acids |
IL136839A (en) | 2000-06-16 | 2006-12-10 | Yissum Res Dev Co | Pharmaceutical compositions comprising cannabidiol derivatives, and processes for the preparation of same |
NZ522349A (en) * | 2000-06-22 | 2004-06-25 | Pharmos Corp | Non-psychotropic cannabinoids that afford neuroprotection by exhibiting anti-inflammatory and/or antioxidative and glutamate-receptor blocking mechanisms of action |
US7235584B2 (en) * | 2000-06-22 | 2007-06-26 | Pharmos Corporation | Non-psychotropic cannabinoids |
DE10051427C1 (de) | 2000-10-17 | 2002-06-13 | Adam Mueller | Verfahren zur Herstellung eines Tetrahydrocannabinol- und Cannabidiol-haltigen Extraktes aus Cannabis-Pflanzenmaterial sowie Cannabis-Extrakte |
US20020111377A1 (en) * | 2000-12-22 | 2002-08-15 | Albany College Of Pharmacy | Transdermal delivery of cannabinoids |
DE10106024B4 (de) | 2001-02-09 | 2004-10-14 | Thc Pharm Gmbh | Verfahren zur Herstellung von Dronabinol |
EP1409473A2 (en) * | 2001-03-07 | 2004-04-21 | Websar Innovations Inc. | CONVERSION OF CBD TO $g(D)?8 -THC AND $g(D)?9 -THC |
GB2377218A (en) | 2001-05-04 | 2003-01-08 | Gw Pharmaceuticals Ltd | Process and apparatus for extraction of active substances and enriched extracts from natural products |
GB0112752D0 (en) | 2001-05-25 | 2001-07-18 | Johnson Matthey Plc | Synthesis of cannabinoids |
GB0112748D0 (en) | 2001-05-25 | 2001-07-18 | Johnson Matthey Plc | Uncatalysed addition reactions |
US20030017216A1 (en) * | 2001-07-23 | 2003-01-23 | Schmidt Robert Gustav | Isolation of herbal and cannabinoid medicinal extracts |
GB2381450B (en) | 2001-10-31 | 2006-05-31 | Gw Pharma Ltd | Compositions for administration of natural or synthetic cannabinoids by vaporisation |
DE60321318D1 (de) * | 2002-02-01 | 2008-07-10 | Resolution Chemicals Ltd | Gewinnung von delta-9 tetrahydrocannabinol |
US7285687B2 (en) | 2002-04-25 | 2007-10-23 | Virginia Commonwealth University | Cannabinoids |
US6946150B2 (en) * | 2002-08-14 | 2005-09-20 | Gw Pharma Limited | Pharmaceutical formulation |
US20040043946A1 (en) * | 2002-09-03 | 2004-03-04 | Popp Karl F. | Topical formulations for treatment of skin disorders |
GB0222077D0 (en) | 2002-09-23 | 2002-10-30 | Gw Pharma Ltd | Methods of preparing cannabinoids from plant material |
GB2393182B (en) | 2002-09-23 | 2007-03-14 | Gw Pharma Ltd | Method of preparing cannabidiol from plant material |
WO2004043946A1 (en) * | 2002-11-12 | 2004-05-27 | Mallinckrodt Inc. | Cannabinoid crystalline derivatives and process of cannabinoid purification |
IL153277A0 (en) * | 2002-12-04 | 2003-07-06 | Pharmos Corp | High enantiomeric purity dexanabinol for pharmaceutical compositions |
US20040248970A1 (en) * | 2003-04-10 | 2004-12-09 | Webster G.R. Barrie | CBD-delta8-THC composition |
EP1613578A2 (en) | 2003-04-10 | 2006-01-11 | Mallinckrodt Inc. | Olivetol-cyclodextrin complexes and regio-selective process for preparing delta 9-tetrahydrocannabinol |
DE602004031221D1 (de) * | 2003-05-20 | 2011-03-10 | Univ Tennessee Res Foundation | Cannabinoidderivate, verfahren zu deren herstellung und deren verwendung |
WO2005100333A1 (en) | 2004-04-07 | 2005-10-27 | Cedarburg Pharmaceuticals, Inc. | Methods and intermediates for the synthesis of delta-9 tetrahydrocannabinol |
GB2414933B (en) | 2004-06-08 | 2009-07-15 | Gw Pharma Ltd | Cannabinoid compositions for the treatment of disease and/or symptoms in arthritis |
CN1997636B (zh) | 2004-07-19 | 2011-09-28 | 希莱格有限公司 | 获得纯四氢大麻酚的方法 |
US7323576B2 (en) * | 2004-10-01 | 2008-01-29 | Alphora Research Inc. | Synthetic route to dronabinol |
TWI369203B (en) | 2004-11-22 | 2012-08-01 | Euro Celtique Sa | Methods for purifying trans-(-)-△9-tetrahydrocannabinol and trans-(+)-△9-tetrahydrocannabinol |
WO2006063109A2 (en) | 2004-12-09 | 2006-06-15 | Insys Therapeutics, Inc. | Room-temperature stable dronabinol formulations |
-
2006
- 2006-09-28 CA CA002623723A patent/CA2623723A1/en not_active Abandoned
- 2006-09-28 CN CN2012102143814A patent/CN102766128A/zh active Pending
- 2006-09-28 EP EP12191321.4A patent/EP2578577A1/en not_active Withdrawn
- 2006-09-28 US US11/529,147 patent/US7674922B2/en not_active Expired - Fee Related
- 2006-09-28 EP EP12191320.6A patent/EP2578561A1/en not_active Withdrawn
- 2006-09-28 NZ NZ601567A patent/NZ601567A/xx not_active IP Right Cessation
- 2006-09-28 AU AU2006297300A patent/AU2006297300B2/en not_active Ceased
- 2006-09-28 NZ NZ594077A patent/NZ594077A/xx not_active IP Right Cessation
- 2006-09-28 NZ NZ567029A patent/NZ567029A/en not_active IP Right Cessation
- 2006-09-28 JP JP2008533571A patent/JP2009510078A/ja active Pending
- 2006-09-28 CN CNA2006800443431A patent/CN101316832A/zh active Pending
- 2006-09-28 KR KR1020087010362A patent/KR20080063800A/ko not_active Application Discontinuation
- 2006-09-28 EP EP06804207A patent/EP1928853A4/en not_active Withdrawn
- 2006-09-28 WO PCT/US2006/037709 patent/WO2007041167A2/en active Application Filing
- 2006-09-28 ZA ZA200802767A patent/ZA200802767B/xx unknown
-
2008
- 2008-03-24 IL IL190388A patent/IL190388A0/en unknown
-
2009
- 2009-11-25 US US12/626,403 patent/US20100069651A1/en not_active Abandoned
-
2011
- 2011-05-16 US US13/108,651 patent/US8106244B2/en active Active
Non-Patent Citations (10)
Title |
---|
ABEL: "Marijuana: The First Twelve Thousand Years", 1980, PLENUM PRESS, pages: 11 - 12 |
DEVANE ET AL., MOL. PHARMACOL., vol. 34, 1988, pages 605 - 613 |
DEVANE ET AL., SCIENCE, vol. 258, 1992, pages 1946 - 1949 |
HERODOTUS: "The Histories, Book IV", 1972, PENGUIN BOOKS, LTD., pages: 295 |
HODJAT-KASHANI ET AL., HETEROCYCLES, vol. 24, 1986, pages 1973 - 1976 |
HUFFMAN ET AL., CURRENT MED. CHEM., vol. 3, 1996, pages 101 - 116 |
MUNRO ET AL., NATURE, vol. 365, 1993, pages 61 - 65 |
RAZDAN: "The Total Synthesis of Natural Products", vol. 4, 1981, WILEY AND SONS, pages: 185 - 262 |
RICKARDS ET AL., TETRAHEDRON LETTERS, vol. 26, no. 8, 1985, pages 1083 - 1086 |
See also references of EP1928853A4 |
Cited By (29)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20110171300A1 (en) * | 2007-02-14 | 2011-07-14 | Resolution Chemicals Limited | Delta 9 tetrahydrocannabinol derivatives |
WO2008099183A1 (en) * | 2007-02-14 | 2008-08-21 | Resolution Chemicals Limited | Delta 9 tetrahydrocannabinol derivatives |
US8530679B2 (en) | 2007-02-20 | 2013-09-10 | Resolution Chemicals Limited | Delta 9—tetrahydrocannabinol processing |
JP2011505382A (ja) * | 2007-11-30 | 2011-02-24 | オールトランツ インコーポレイティド | テトラヒドロカンナビノールのプロドラッグ、テトラヒドロカンナビノールのプロドラッグを含む組成物、及び同一のものを使用する方法 |
US8227627B2 (en) | 2007-11-30 | 2012-07-24 | Alltranz Inc. | Prodrugs of tetrahydrocannabinol, compositions comprising prodrugs of tetrahydrocannabinol and methods of using the same |
JP2014144990A (ja) * | 2007-11-30 | 2014-08-14 | Alltranz Inc | テトラヒドロカンナビノールのプロドラッグ、テトラヒドロカンナビノールのプロドラッグを含む組成物、及び同一のものを使用する方法 |
US8980942B2 (en) | 2007-11-30 | 2015-03-17 | Zynerba Pharmaceuticals, Inc. | Prodrugs of tetrahydrocannabinol, compositions comprising prodrugs of tetrahydrocannabinol and methods of using the same |
JP2016028049A (ja) * | 2007-11-30 | 2016-02-25 | ジネルバ ファーマシューティカルズ, インコーポレイティド | テトラヒドロカンナビノールのプロドラッグ、テトラヒドロカンナビノールのプロドラッグを含む組成物、及び同一のものを使用する方法 |
US9695143B2 (en) | 2007-11-30 | 2017-07-04 | Zynerba Pharmaceuticals, Inc. | Prodrugs of tetrahydrocannabinol, compositions comprising prodrugs of tetrahydrocannabinol and methods of using the same |
US9957246B2 (en) | 2007-11-30 | 2018-05-01 | Zynerba Pharmaceuticals, Inc. | Prodrugs of tetrahydrocannabinol, compositions comprising prodrugs of tetrahydrocannabinol and methods of using the same |
WO2009073633A1 (en) * | 2007-11-30 | 2009-06-11 | Alltranz Inc. | Prodrugs of tetrahydrocannabinol, compositions comprising prodrugs of tetrahydrocannabinol and methods of using the same |
WO2009099868A1 (en) * | 2008-02-06 | 2009-08-13 | Mallinckrodt Inc. | Process for the preparation of (-) -delta 9-tetrahydrocannabinol |
EP3253727A4 (en) * | 2015-02-05 | 2018-08-08 | Colorado Can LLC | Purified cbd and cbda, and methods, compositions and products employing cbd or cbda |
US11168047B2 (en) | 2017-08-07 | 2021-11-09 | Enantia, S.L. | Cocrystal of 2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-5-pentylbenzene-l,3-diol |
WO2019030158A1 (en) | 2017-08-07 | 2019-02-14 | Enantia, S.L. | CO-CRYSTAL OF 2 - [(1R, 6R) -6-ISOPROPENYL-3-METHYLCYCLOHEX-2-EN-1-YL] -5-PENTYLBENZENE-1,3-DIOL |
WO2019033168A1 (en) * | 2017-08-16 | 2019-02-21 | The University Of Sydney | SYNTHESIS OF PHYTOCANNABINOIDS COMPRISING A DECARBOXYLATION STAGE |
US10807931B2 (en) | 2017-08-16 | 2020-10-20 | The University Of Sydney | Synthesis of phytocannabinoids including a decarboxylation step |
AU2018317939B2 (en) * | 2017-08-16 | 2021-06-03 | The University Of Sydney | Synthesis of phytocannabinoids including a decarboxylation step |
EP3539637A1 (en) * | 2018-03-13 | 2019-09-18 | CLS Labs, Inc. | Cannabidiol extraction and conversion process |
US20210106929A1 (en) * | 2018-08-10 | 2021-04-15 | Natural Extraction Systems, LLC | Methods to purify cannabinoids |
US11702397B2 (en) * | 2018-08-10 | 2023-07-18 | Natural Extraction Systems, LLC | Methods to purify cannabinoids |
WO2020089424A1 (en) | 2018-10-31 | 2020-05-07 | Enantia, S.L. | Solid compositions of cocrystals of cannabinoids |
WO2020198876A1 (en) * | 2019-04-05 | 2020-10-08 | Rapid Dose Therapeutics Corp. | Apparatus for and method of converting cbd and/or cbd derivatives to at least one other type of cannabinoid and/or cannabinoid derivative such as thc |
WO2020232526A1 (en) * | 2019-05-17 | 2020-11-26 | Nextleaf Solutions Ltd | Method for acetylation of cannabinoids |
EP3983395A4 (en) * | 2019-06-11 | 2023-10-18 | Canopy Growth Corporation | IMPROVED PROCESSES FOR CONVERTING CANNABIDIOL TO DELTA 8-TETRAHYDROCANNABINOL |
WO2021046630A1 (en) * | 2019-09-15 | 2021-03-18 | Nextleaf Solutions Ltd | Acetylation of cannabinoids using sulfuric acid catalyst |
WO2021181420A1 (en) | 2020-03-12 | 2021-09-16 | Council Of Scientific And Industrial Research An Indian Registered Body Incorporated Under The Regn. Of Soc. Act (Act Xxi Of 1860) | Process for the synthesis of cannabidiol and intermediates thereof |
WO2021198692A1 (en) | 2020-03-31 | 2021-10-07 | Phytotherapeutix Ltd | Terpenophenolic compounds and their use |
WO2024028516A1 (en) | 2022-08-05 | 2024-02-08 | Salud & Semillas, S.L. | CANNABINOID SYNTHESIS STARTING OUT FROM OLIVETOL AND TERPENE IN DICHLOROMETHANE WITH FeCl3 * 6H2O AS CATALYST |
Also Published As
Publication number | Publication date |
---|---|
US7674922B2 (en) | 2010-03-09 |
US20110263878A1 (en) | 2011-10-27 |
WO2007041167A3 (en) | 2007-11-22 |
EP1928853A2 (en) | 2008-06-11 |
AU2006297300B2 (en) | 2012-05-10 |
CA2623723A1 (en) | 2007-04-12 |
ZA200802767B (en) | 2009-09-30 |
JP2009510078A (ja) | 2009-03-12 |
IL190388A0 (en) | 2008-11-03 |
NZ594077A (en) | 2013-02-22 |
US8106244B2 (en) | 2012-01-31 |
AU2006297300A1 (en) | 2007-04-12 |
US20100069651A1 (en) | 2010-03-18 |
EP2578561A1 (en) | 2013-04-10 |
EP2578577A1 (en) | 2013-04-10 |
KR20080063800A (ko) | 2008-07-07 |
NZ601567A (en) | 2013-03-28 |
EP1928853A4 (en) | 2011-02-16 |
CN101316832A (zh) | 2008-12-03 |
NZ567029A (en) | 2011-09-30 |
US20070093665A1 (en) | 2007-04-26 |
CN102766128A (zh) | 2012-11-07 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
AU2006297300B2 (en) | Process for production of delta-9-tetrahydrocannabinol | |
EP2044076B1 (en) | Process for the preparation of asenapine and intermediate products used in said process. | |
CA2751741C (en) | Process for the preparation of (-) -delta 9-tetrahydrocannabinol | |
Nemoto et al. | Enantioselective total syntheses of (+)-decursin and related natural compounds using catalytic asymmetric epoxidation of an enone | |
CN112592260A (zh) | 一种大麻二酚的合成方法 | |
US6444826B1 (en) | Processes and intermediates for preparing substituted chromanol derivatives | |
AU2012201041B2 (en) | Process for production of delta-9-tetrahydrocannabinol | |
US20070287843A1 (en) | Methods and Intermediates for the Synthesis of Delta-9 Tetrahydrocannabinol | |
US7153994B2 (en) | Manufacture of trimethylhydroquinone diacylates | |
WO2012080243A2 (en) | Novel process | |
WO2014111903A2 (en) | A process for the preparation of 6-fluoro-3,4-dihydro-2h-chromene- 2-carbaldehyde | |
Sugimura et al. | Chiral and flexible 2, 4-pentanediol-tethered cyclopropanation of olefins with a carbenoid derived from a diazo ester to construct three stereogenic centers | |
CN107188786B (zh) | 一种医药中间体光学纯环戊烯醇的制备方法 | |
JPS6289660A (ja) | 4−オキソ−4,5,6,7−テトラヒドロインド−ルの製法 | |
KR0150292B1 (ko) | 피라졸을 함유한 프로페노익 에스테르 유도체의 신규한 제조방법 | |
EP2003112A1 (en) | Method for producing carboxylic acid compound | |
WO2023122754A1 (en) | Processes and intermediates for preparing gb13, gb22 and himgaline | |
CN116199607A (zh) | 毛果芸香碱及其中间体化合物的制备方法 | |
US8258322B2 (en) | Synthesis of hexahydrodibenzopyranones | |
HANAOKA et al. | Chemical Transformation of Protoberberines. XIV. Acid-Catalyzed Cleavage of 8-Alkyl-8, 14-cycloberbines. A Simple Method for the Preparation of N-Unsubstituted Spirobenzylisoquinolines | |
JPH07242572A (ja) | ジメチルヘプタトリアコンタンおよびその類似体の製造方法 | |
JPH0211585A (ja) | クロマン誘導体の製造方法 | |
MXPA01010768A (en) | Processes and intermediates for preparing substituted chromanol derivatives |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
WWE | Wipo information: entry into national phase |
Ref document number: 200680044343.1 Country of ref document: CN |
|
121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
WWE | Wipo information: entry into national phase |
Ref document number: 190388 Country of ref document: IL |
|
ENP | Entry into the national phase |
Ref document number: 2623723 Country of ref document: CA |
|
WWE | Wipo information: entry into national phase |
Ref document number: 1510/CHENP/2008 Country of ref document: IN Ref document number: 2006804207 Country of ref document: EP |
|
ENP | Entry into the national phase |
Ref document number: 2008533571 Country of ref document: JP Kind code of ref document: A |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2006297300 Country of ref document: AU Ref document number: 567029 Country of ref document: NZ |
|
NENP | Non-entry into the national phase |
Ref country code: DE |
|
ENP | Entry into the national phase |
Ref document number: 2006297300 Country of ref document: AU Date of ref document: 20060928 Kind code of ref document: A |
|
WWE | Wipo information: entry into national phase |
Ref document number: 1020087010362 Country of ref document: KR |