6,12-Dihydro-6-hydroxy-cannabidiol

The compound 6,12-dihydro-6-hydroxy-cannabidiol described in the present application has so far not been either synthetically produced or used as an intermediate for the production of irans-delta-9-tetrahy-drocEmnabinol. One reference to it in the literature (see Garrett et al., J. Pharm. Sci. 67 (1978) pages 27-32) only relates to the analytical chromatographic trace detection of one of a number of many other products of decomposition of delta-9-THC in an acidic solution. The compound has therefore not been produced in preparative quantities nor used for any sort of reactions. Furthermore the physical data of the compound have not been described previous to the present application. 

In accordance with the invention the first step is to produce the intermediate 6,12-dihydro-6-hydroxy-cannabidiol which may also be termed 1,3-dihydroxy-2-[6-(l -hydroxy-1 -methyl-ethyl)-3-methyl-2-cyclohexene-l-yl]-5-pentyl-benzene. This compound is denoted I in the above scheme. 

For the synthesis of 6,12-dihydro-6-hydroxy-cannabidiol as the intermediate in accordance with the invention the starting materials are the readily available olivetol (formula II) and cis-p-menth-2-ene-l,8-diol (formula III). The reaction is performed in a suitable solvent, aromatic hydrocarbons such as benzene and toluene, halogenated hydrocarbons such as methylene chloride, chloroform, dichloroethane and trichloroethane, ethers such as diethylether, diisopropylether and tetrahydrofuran having proved to be suitable. Furthermore it is possible to use mixtures of the said solvents. Toluene, benzene, methylene chloride and chloroform are the preferred solvents for use in the method of the invention. 

It is an advantage in the method in accordance with the invention that starting with readily available materials the intermediate product in the form of 6,12-dihydro-6-hydroxy-cannabidiol may be produced simply with a good yield and that such product may be purified without any great difficulty. 

The petroleum ether phase was then run into a silica gel column (approximately 500 g of silica gel) and eluted with a mixture of petroleum ether (50/70) and diisopropylether (2 1). The eluate was reduced in volume under vacuum and the residue (approximately 102 g) was recrystallized from 600 mL of petroleum ether (50/70). 77 g of the desired product were obtained. The characteristic data of the 6,12-dihydro-6-hydroxy-cannabidiol were as follows Fusion point 77° to 77.5° C. 

Stoss, P. Merrath, P. Method for the Production of 6,12-dihydro-6-hydroxy-cannabidiol and the use Thereof for the Production of trans-delta-9-tetrahydro-cannabinol 1992 EP0494665... 

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