US 12,234,203 B2
Process for the synthesis of cannabidiol and intermediates thereof
Radhika Anand, Jammu Jammu Kashmir (IN); Sumit Sharma, Jammu Jammu Kashmir (IN); Pankaj Singh Cham, Jammu Jammu Kashmir (IN); Veeranjaneyulu Gannedi, Jammu Jammu Kashmir (IN); Mukesh Kumar, Jammu Jammu Kashmir (IN); Varun Pratap Singh, Jammu Jammu Kashmir (IN); Vishav Prakash Rahul, Jammu Jammu Kashmir (IN); Ram Asrey Vishwakarma, Jammu Jammu Kashmir (IN); and Parvinder Pal Singh, Jammu Jammu Kashmir (IN)
Assigned to COUNCIL OF SCIENTIFIC AND INDUSTRIAL RESEARCH AN INDIAN REGISTERED BODY INCORPORATED UNDER THE REGN. OF SOC. ACT (ACT XXI OF 1860), New Delhi (IN)
Appl. No. 17/594,448
Filed by COUNCIL OF SCIENTIFIC AND INDUSTRIAL RESEARCH AN INDIAN REGISTERED BODY INCORPORATED UNDER THE REGN. OF THE SOC. ACT (ACT XXI OF 1860), New Delhi (IN)
PCT Filed Mar. 11, 2021, PCT No. PCT/IN2021/050242
§ 371(c)(1), (2) Date Oct. 15, 2021,
PCT Pub. No. WO2021/181420, PCT Pub. Date Sep. 16, 2021.
Claims priority of application No. 202011010503 (IN), filed on Mar. 12, 2020.
Prior Publication US 2022/0340507 A1, Oct. 27, 2022
Int. Cl. C07C 29/00 (2006.01); C07C 37/14 (2006.01); C07C 37/48 (2006.01); C07C 41/01 (2006.01); C07C 67/00 (2006.01); C07C 391/02 (2006.01)
CPC C07C 29/00 (2013.01) [C07C 37/14 (2013.01); C07C 37/48 (2013.01); C07C 41/01 (2013.01); C07C 67/00 (2013.01); C07C 391/02 (2013.01); C07C 2601/10 (2017.05)] 5 Claims
 
1. A process for the preparation of cannabidiol compound of formula (A)

OG Complex Work Unit Chemistry
comprising the steps of:
(a) contacting a compound of formula (B) with a reagent selected from PhSeBr, PhSeCl, PhSCI, PhSBr, PhSSPh/AgOTf, PhSSPh/N-Chloromethyl-N′-fluorotriethylenediammonium bis(tetrafluoroborate), PhSeSePh/AgOTf, or PhSeSePh/N-Chloromethyl-N′-fluorotriethylenediammonium bis(tetrafluoroborate),
in the presence of a solvent or a mixture of solvents selected from H2O, tetrahydrofuran, dioxane, acetonitrile, chlorobenzene, dichloroethane, acetone, hexane, dichloromethane, chloroform, ethyl acetate, and toluene; and with stirring for a time period in the range of 0.1 h-48 h and at a temperature in the range of −80° C. to 60° C., whereby a compound of formula (C) is produced;
(b) contacting the compound of formula (C) with an oxidant selected from mCPBA, Oxone, DDQ, CAN, N-hydroxy succinamide, t-Butylhydroperoxide, N-Chloromethyl-N′-fluorotriethylenediammonium bis(tetrafluoroborate), Hydrogen peroxide, BIAB, NFSI, TMSOTf, PyF-BF4, PyF-OTf, TMPyF-OTf, and PIFA,
in the presence of a solvent or a mixture of solvents selected from H2O, tetrahydrofuran, dioxane, acetonitrile, chlorobenzene, dichloroethane, acetone, hexane, dichloromethane, chloroform, ethyl acetate, and toluene; and with stirring the for a time period in the range of 0.1 to 48 hours at a temperature in the range of −40° C. to 60° C., whereby a compound of formula (D) is produced;
(c) contacting the compound of formula (D) with a compound of formula (E) in the presence of
(i) a metal triflate selected from AgOTf, Ni(OTf)2, Hg(OTf)2, LiOTf, Bi(OTf)3, Ln(OTf)3, and Ac(OTf)x, optionally in the presence of a ligand selected from bipyridyl, substituted bipyridyl phenanthrolene, substituted phenanthrolene, pyridine, substituted pyridine, BINAP, QINAP, PINAP, Ph3P; or
(ii) a heterogeneous acid selected from mixed metal oxides, SiO2—SO3H/COFe2O4, SiO2—Pr—SO3H, zeolites, zeotype materials, OMR-[C4HMTA][SO3H], MPD-SO3H-IL, MeAPSO, MeAPO, SAPO, ALPO4, Natrolite, ZSM-5, H-ZSM-5, periodic mesoporous organosilicas (PMOs), mesoporous silicas (PMSs), H3PW12O40, H4SiW12O40, Cs2HPW12O40, HPW/ZrO2, HPW/Nb2O5, Montmorillonite, pyrophyllite, Talc, Vermiculite, Sauconite, Saponite, Nontronite, Kaolinite, Chlorite, Illite, SAPO-34, Zirconium phosphates or sulphates, cation/anion exchange resins, amberlyst, and amberlite;
in the presence of a solvent or mixture of solvents selected from tetrahydrofuran, dioxane, acetonitrile, chlorobenzene, dichloroethane, acetone, hexane, dichloromethane, chloroform, ethyl acetate, and toluene; and with stirring for time period in the range of 0.1 to 48 hours at a temperature in the range of −40° C. to 60° C.;
wherein
R is independently selected from H, OH, alkyl, alkenyl, alkynyl, and cycloalkyl;
R1, R2, R3 and R4 are independently selected from H, OH, alkyl, alkenyl, alkynyl, acyl, acyloxy, and cycloalkyl;
X is independently selected from OH, H, heteroaryl, Cl, Br, I, OTf, OTs, and phosphinyl;
Y is independently selected from S and Se;
wherein, each custom character represents a single or double bond; provided that both custom character groups are not double bonds, and wherein denoted, dash marks indicate the points of attachment;
wherein, custom character represents a single bond, above the plane or below the plane or both above the plane or both below the plane or one is above the plane and one is below the plane.