# US 11,897,895 B2 · Process for preparing 2-exo-(2-Methylbenzyloxy)-1-methyl-4-isopropyl-7-oxabicy-clo[2.2.1]heptane > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,897,895 B2 - Document ID: US11897895B2 - Status: Granted - Kind: B2 - Application number: 16/770,969 - Filed: 2018-12-06 - Published: 2021-06-03 - Granted: 2024-02-13 - Earliest claimed: 2017-12-15 - Assignees: BASF Agro B.V. - Applicants: BASF Agro B.V. - Inventors: Michael Rack; Stefan Benson; Bernd Wolf; Roland Goetz - Web page: https://patentgrep.com/patent/US11897895B2 ## CPC - C07D 493/18: Bridged systems - C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08) ## Abstract This invention relates to a process for preparing (±)-2-exo-(2-Methylbenzyloxy)-1-methyl-4-isopropyl-7-oxabicyclo[2.2.1]heptane of the formula (I), any one of its individual enantiomers or any non-racemic mixture thereof any one of its individual enantiomers or any non-racemic mixture thereof, comprising the steps of (a) reacting (±)-2-exo-hydroxy-1-methyl-4-isopropyl-7-oxabicyclo[2.2.1]heptane of the formula (II), any one of its individual enantiomers or any non-racemic mixture thereof (as defined in the description) with elemental sodium to form a sodium salt of the formula (III), any one of its individual enantiomers or any non-racemic mixture thereof (as defined in the description), and (b) reacting said sodium salt (III) with a 2-Methylbenzyl compound of the formula (IV) wherein X is a leaving group, wherein the steps (a) and (b) are conducted in the presence of at least one substantially anhydrous inert organic solvent. ## Claims ### Claim 1 A process for preparing (±)-2-exo-(2-Methylbenzyloxy) -1-methyl-4-isopropyl-7-oxabicyclo[2.2.1]heptane of the formula (I) any one of its individual enantiomers or any non-racemic mixture thereof comprising the steps of (a) reacting (±)-2-exo-hydroxy-1-methyl-4-isopropyl-7-oxabicyclo[2.2.1]heptane of the formula (II) any one of its individual enantiomers or any non-racemic mixture thereof with elemental sodium to form a sodium salt of the formula (III) any one of its individual enantiomers or any non-racemic mixture thereof, and (b) reacting the sodium salt of the formula (III), any of its individual enantiomers or any non-racemic mixture thereof with a 2-Methylbenzyl compound of the formula (IV) wherein X is a leaving group, wherein the steps (a) and (b) are conducted in the presence of at least one substantially anhydrous inert organic solvent selected from hydrocarbons, wherein the substantially anhydrous inert organic solvent has a water content lower than 0.1% by weight (Based on a total weight of the substantially anhydrous inert organic solvent, and wherein the elemental sodium used in step (a) is present in the form of dispersed sodium particles and step (b) is conducted in the presence of at least one phase transfer catalyst selected from quaternary phosphonium salts. ### Claim 2 (depends on 1) The process according to claim 1, wherein the substantially anhydrous inert organic solvent is selected from aliphatic hydrocarbons, cycloaliphatic hydrocarbons, aromatic hydrocarbons and any combination thereof. ### Claim 3 (depends on 1) The process according to claim 1, wherein the substantially anhydrous inert organic solvent is selected from n-heptane, n-octane, cycloheptane, cyclooctane, toluene, o-xylene, m-xylene, p-xylene, ethylbenzene, 2-propylbenzene (cumene), 2-isopropyltoluene (o-cymol), 3-isopropyltoluene (m-cymol), 4-isopropyltoluene (p-cymol), 1,3,5-trimethylbenzene (mesitylene) and any combination thereof. ### Claim 4 (depends on 1) The process according to claim 1, wherein the elemental sodium used in step (a) is present in the form of a dispersion of sodium particles in an inert dispersing medium. ### Claim 5 (depends on 4) The process according to claim 4, wherein the inert dispersing medium of the dispersion of sodium particles is identical to the substantially anhydrous inert organic solvent used in steps (a) and (b). ### Claim 6 (depends on 1) The process according to claim 1, wherein the substantially anhydrous inert organic solvent and/or the inert dispersing medium has a boiling point of equal to or more than the melting point of sodium (97.7° C.). ### Claim 7 (depends on 1) The process according to claim 1, wherein the substantially anhydrous inert organic solvent has a water content lower than 0.01% by weight (based on the total weight of the substantially anhydrous inert organic solvent). ### Claim 8 (depends on 1) The process according to claim 1, wherein the molar ratio of the elemental sodium (calculated as 100% Na) to (±)-2-exo-hydroxy-1-methyl-4-isopropyl-7-oxabicyclo[2.2.1]heptane of the formula (II), any one of its individual enantiomers or any non-racemic mixture thereof is from 0.95:1 to 5:1. ### Claim 9 (depends on 1) The process according to claim 1, wherein the phase transfer catalyst is selected from quaternary phosphonium salts of general formula (VII) (R8R9R10R11P)+Z2− (VII) wherein R8, R9, R10, and R11 are the same or different and are each independently selected from a 5- or 6-membered heterocyclyl group containing 1, 2 or 3 heteroatoms selected from the group consisting of O, N and S, and Z2− is a monovalent anion. ### Claim 10 (depends on 1) The process according to claim 1, wherein the phase transfer catalyst is tetrakis(1-piperidyl)phosphonium chloride. ### Claim 11 (depends on 1) The process according to claim 1, wherein X is halogen. ### Claim 12 (depends on 1) The process according to claim 1, wherein the 2-Methylbenzyl compound of the formula (IV) is 2-Methylbenzyl chloride of the formula (IVa) ### Claim 13 (depends on 1) The process according to claim 1, wherein the substantially anhydrous inert organic solvent is selected from aromatic hydrocarbons. ### Claim 14 (depends on 3) The process according to claim 3, wherein the substantially anhydrous inert organic solvent is toluene. ### Claim 15 (depends on 7) The process according to claim 7, wherein the substantially anhydrous inert organic solvent has a water content lower than 0.0001% by weight (based on the total weight of the substantially anhydrous inert organic solvent). ### Claim 16 (depends on 9) The process according to claim 9, wherein the monovalent anion Z2− is selected from the group consisting of a halide, hydroxide, hydrogen sulfate, and monomethyl sulfate. ### Claim 17 (depends on 9) The process according to claim 9, wherein the monovalent anion Z2− is selected from the group consisting of chloride, bromide, iodide, and hydroxide. ### Claim 18 (depends on 9) The process according to claim 9, wherein the monovalent anion Z2− is chloride.