# US 10,501,434 B2 · Configurational stereoisomer of difethialone, composition and rodenticidal bait comprising same, and process for controlling target rodent pests > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,501,434 B2 - Document ID: US10501434B2 - Status: Granted - Kind: B2 - Application number: 16/061,084 - Filed: 2016-12-06 - Published: 2018-12-20 - Granted: 2019-12-10 - Earliest claimed: 2015-12-11 - Assignees: Liphatech; Institut Enseignement Superieur Et Recherche En Alimentation Sante Animale Sciences Agronomiques Et Environnement (Vet Agro Sup) - Applicants: Liphatech; Institut Enseignement Superieur Et Recherche En Alimentation Sante Animale Sciences Agronomiques Et Environnement (Vet Agro Sup) - Inventors: Hervé Caruel; Etienne Benoit; Isabelle Fourel; Virginie Lattard - Web page: https://patentgrep.com/patent/US10501434B2 ## CPC - C07D 335/06: Benzothiopyrans; Hydrogenated benzothiopyrans - A01N 25/004: {rodenticidal} - A01N 43/18: with sulfur as the ring hetero atom - B01D 15/3833: {Chiral chromatography} - C07B 2200/07: Optical isomers - C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08) - A01N: PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF (preservation of food or foodstuff A23); BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES (preparations for medical, dental or toiletry purposes which kill or prevent the growth or proliferation of unwanted organisms A61K); PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS - B01D: SEPARATION (separating solids from solids by wet methods B03B, B03D; by pneumatic jigs or tables B03B; by other dry methods B07; magnetic or electrostatic separation of solid materials from solid materials or fluids, separation by high-voltage electric fields B03C; centrifuges, vortex apparatus B04; presses per se for squeezing-out liquid from liquid-containing material B30B9/02; treatment of water C02F, e.g. softening by ion-exchange C02F1/42; {arrangements of air intake cleaners in gas turbine plants F02C7/05} ; arrangements or mounting of filters in air-conditioning, air-humidification or ventilation F24F13/28) - C07B: GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR (preparation of carboxylic acid esters by telomerisation C07C67/47; telomerisation C08F) ## Abstract Disclosed is to a laevorotatory enantiomer of the configurational stereoisomer of difethialone, named hetero-stereoisomer, the formula of which is 3-(4′-bromobiphenyl-4-yl)-1-(4-hydroxythiocoumarin-3-yl)-1,2,3,4-tetrahydronaphthalene, in which carbons 1 and 3 of the 1,2,3,4-tetrahydronaphthalene group have different absolute configurations. ## Claims ### Claim 1 Laevorotatory enantiomer of a configurational stereoisomer of difethialone, named hetero-stereoisomer, the formula of which is 3-(4′-bromobiphenyl-4-yl)-1-(4-hydroxythiocoumarin-3-yl)-1,2,3,4-tetrahydronaphthalene, in which carbons 1 and 3 of the 1,2,3,4-tetrahydronaphthalene group have different absolute configurations, said laevorotatory enantiomer of said hereto-stereoisomer of difethialone being in isolated form. ### Claim 2 Composition comprising the laevorotatory enantiomer of the configurational stereoisomer of difethialone, named hetero-stereoisomer, the formula of which is 3-(4 -bromobiphenyl-4-yl)-1-(4-hydroxythiocoumarin-3-y;)-1,2,3,4-tetrahydronaphthalene, in which carbons 1 and 3 of the 1,2,3,4-tetrahydronaphthalene group have different absolute configurations, with the exclusion of a racemic mixture of laevorotatory and dextrorotatory enantiomers of said hetero-stereoisomer of difethialone. ### Claim 3 (depends on 2) Composition according to claim 2, wherein said hetero-stereoisomer is predominantly in laevorotatory enantiomer form. ### Claim 4 (depends on 2) Composition according to claim 2, wherein the difethialone is predominantly in the laevorotatory enantiomer form of said hetero-stereoisomer of difethialone. ### Claim 5 (depends on 2) Composition according to claim 2, comprising an amount of the laevorotatory enantiomer of said hetero-stereoisomer of difethialone such that the ratio of this amount to the amount of difethialone is greater than 25%. ### Claim 6 (depends on 2) Composition according to claim 2, comprising an amount of the laevorotatory enantiomer of said hetero-stereoisomer of difethialone such that the ratio of this amount to the amount of difethialone is greater than 97% in the composition. ### Claim 7 (depends on 2) Rodenticidal bait comprising a composition according to claim 2 and at least one excipient that is edible for target rodent pests. ### Claim 8 (depends on 7) Bait according to claim 7, wherein the edible excipient comprises at least one food chosen from the group formed from cereal seeds, cereal seed meals, cereal seed flours, cereal seed flakes, cereal bran and non-cereal seeds. ### Claim 9 (depends on 7) Bait according to claim 7, comprising a mass amount of difethialone such that the ratio of this mass amount of difethialone to the mass amount of rodenticidal bait is less than 200 ppm. ### Claim 10 Process for controlling target rodent pests, in which there is spread an amount of bait comprising: at least one excipient that is edible for target rodent pests; and the laevorotatory enantiomer of the configurational stereoisomer of difethialone, named hetero-stereoisomer, the formula of which is 3-(4′-bromobiphenyl-4-yl)-1-(4-hydroxythiocoumarin-3-yl)-1,2,3,4-tetrahydronaphthalene, in which carbons 1 and 3 of the 1,2,3,4-tetrahydronaphthalene group have different absolute configurations; with the exclusion of a racemic mixture of the laevorotatory and dextrorotatory enantiomers of said hetero-stereoisomer of difethialone. ### Claim 11 (depends on 10) Process according to claim 10, wherein said hetero-stereoisomer of difethialone is predominantly in laevorotatory enantiomer form. ### Claim 12 (depends on 10) Process according to claim 10, wherein the difethialone is predominantly in the laevorotatory enantiomer form of said hetero-stereoisomer of difethialone. ### Claim 13 (depends on 10) Process according to claim 10, wherein the following are chosen in combination: the edible excipient; a proportion of laevorotatory enantiomer of said hetero-stereoisomer of difethialone relative to said hetero-stereoisomer of difethialone; a proportion of laevorotatory enantiomer of said hetero-stereoisomer of difethialone relative to the difethialone; a mass proportion of difethialone relative to the rodenticidal bait; and an amount of spread bait; so that target rodent pests consume an amount of difethialone that is sufficient to be lethal to said target rodent pests which consume said bait in the course of a single period of 24 consecutive hours. ### Claim 14 (depends on 10) Process according to claim 10, wherein the following are chosen in combination: the edible excipient; a proportion of laevorotatory enantiomer of said hetero-stereoisomer of difethialone relative to said hetero-stereoisomer of difethialone; a proportion of laevorotatory enantiomer of said hetero-stereoisomer of difethialone relative to the difethialone; a mass proportion of difethialone relative to the rodenticidal bait; and an amount of spread bait; so that target rodent pests consume an amount of difethialone: which is non-lethal to target rodent pests which consume said bait over a period of 24 consecutive hours; and which is sufficient to be lethal to target rodent pests which consume said bait over several 24-hour periods, said periods being consecutive. ### Claim 15 Chromatographic process for obtaining a laevorotatory enantiomer of a configurational stereoisomer of difethialone, named hetero-stereoisomer, the formula of which is 3-(4′-bromobiphenyl-4-yl)-1-(4-hydroxythiocoumarin-3-yl)-1,2,3,4-tetrahydronaphthalene, in which carbons 1 and 3 of the 1,2,3,4-tetrahydronaphthalene group of said hetero-stereoisomer have different absolute configurations, in which process: a high-pressure liquid chromatography column of dimensions 150×2 mm, and comprising a chiral stationary phase constituted of particles of tris(4-methylbenzoate) cellulose, said particles having a mean size of 3 μm and having a mean pore size of 1000 Å, is chosen; a mixture formed from acetonitrile (A) and water comprising 0.1% by volume of formic acid (B), with an A/B volume ratio of 80/20 and with a flow rate of the liquid mobile phase in the chromatography column of 0.25 mL/minute, is chosen as liquid mobile phase; separation of the configurational stereoisomers of difethialone is performed at room temperature, during which: a liquid composition comprising said laevorotatory enantiomer of said hetero-stereoisomer of difethialone is introduced into the top of the chromatography column; and then the liquid composition is entrained with the mobile phase in the chromatography column under conditions suitable for separating the configurational stereoisomers of difethialone; and a fraction of the mobile phase comprising said laevorotatory enantiomer of said hetero-stereoisomer of difethialone is collected with a retention time t2 having a value such that t1