# US 10,501,410 B2 · Pocess for the preparation of high purity prostaglandins > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,501,410 B2 - Document ID: US10501410B2 - Status: Granted - Kind: B2 - Application number: 15/117,092 - Filed: 2015-03-11 - Published: 2017-02-09 - Granted: 2019-12-10 - Earliest claimed: 2014-03-13 - Assignees: Chinoin GyóGyszer éS VegyéSzeti TerméKek GyáRa Zrt. - Applicants: Chinoin GyóGyszer éS VegyéSzeti TerméKek GyáRa Zrt. - Inventors: Ervin Vajda; Irén Hortobágyi; István Lászlofi; Péter Buzder-Lantos; Gábor Havasi; László Takács; Zsuzsanna Kardos - Web page: https://patentgrep.com/patent/US10501410B2 ## CPC - C07C 405/00: Compounds containing a five-membered ring having two side-chains in ortho position to each other, and having oxygen atoms directly attached to the ring in ortho position to one of the side-chains, one side-chain containing, not directly attached to the ring, a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, and the other side-chain having oxygen atoms attached in gamma-position to the ring, e.g. prostaglandins {; Analogues or derivatives thereof} - B01D 15/322: {Normal bonded phase} - C07C 2601/08: the ring being saturated - C07C: ACYCLIC OR CARBOCYCLIC COMPOUNDS - 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) ## Abstract The subject of the invention is a process for the preparation of high purity prostaglandin acid of the general formula II wherein the bonds marked with dotted lines represent single or double bonds wherein the double bonds may be cis- or trans oriented, Y represents O or CH2, and R3 stands for a phenyl group which is optionally substituted with CF3, wherein the crude prostaglandin acid of the general formula II is purified by normal phase silicagel chromatography. ## Claims ### Claim 1 A process for the purification of latanoprost acid of Formula IIa: which consists of purifying crude latanoprost acid of Formula IIa by gravitational chromatography on a normal phase chromatography column filled with silica gel so that the purified latanoprost acid of Formula IIa has a purity of 89.9%-99.5% and isomeric impurities of trans-latanoprost acid and 15-epi-latanoprost acid obtained in the process are not individually more than 0.15%, wherein a multicomponent eluent mixture is applied as eluent, and wherein the eluent mixture contains one or more apolar solvents, one or more polar solvents and solvent of acidic character, in a ratio of (91-73%):(24-8.7%):(0.1-4.3%). ### Claim 2 (depends on 1) The process as defined in claim 1, wherein the applied silica gel is a spherical silica gel having average particle size in a range of 75-150 micrometer. ### Claim 3 (depends on 1) The process as defined in claim 1, wherein the apolar component of the eluent mixture is straight or branched open-chain or cyclic or aromatic hydrocarbon, optionally containing one or more substituents. ### Claim 4 (depends on 3) The process as defined in claim 3, wherein the substituent is halogen atom. ### Claim 5 (depends on 3) The process as defined in claim 3, wherein as apolar solvent aliphatic hydrocarbon is applied. ### Claim 6 (depends on 1) The process as defined in claim 1, wherein as polar solvent an alcohol-, ether-, ester- or ketone-type solvent is applied which contains straight or branched open-chain alkyl, alkenyl or cyclic or cycloalkyl group. ### Claim 7 (depends on 6) The process as defined in claim 6, wherein as polar solvent C1-5 alcohol is applied. ### Claim 8 (depends on 7) The process as defined in claim 7, wherein as polar solvent isopropyl alcohol is applied. ### Claim 9 (depends on 1) The process as defined in claim 1, wherein the solvent of acidic character of the solvent mixture is an organic acid optionally containing halogen substituent. ### Claim 10 (depends on 9) The process as defined in claim 9, wherein as organic acid a C1-3 organic acid is applied. ### Claim 11 (depends on 1) The process as defined in claim 1, wherein hexane:isopropanol:acetic acid mixture is applied as an eluent. ### Claim 12 (depends on 5) The process as defined in claim 5, wherein the aliphatic hydrocarbon is selected from the group consisting of pentane, hexane, heptane, octane, and cyclohexane. ### Claim 13 (depends on 11) The process as defined in claim 11, wherein the hexane:isopropanol:acetic acid mixture is in a ratio of (91-73%):(24-8.7%):(0.1-4.3%). ### Claim 14 (depends on 1) The process as defined in claim 1, wherein hexane:isopropanol:formic acid, hexane:isopropanol:trifluoro acetic acid, c-hexane:isopropanol:acetic acid, pentane:isopropanol:acetic acid, isooctane:isopropanol:acetic acid, hexane:dichloromethane:isopropanol, or diisopropyl ether:acetone:water is applied as an eluent. ### Claim 15 (depends on 14) The process as defined in claim 14, wherein the eluent is in a ratio of (91-73%):(24-8.7%):(0.1-4.3%). ### Claim 16 (depends on 1) The process as defined in claim 1, wherein the purified latanoprost acid of Formula IIa has a purity of 98.95-99.5%. ### Claim 17 (depends on 1) The process as defined in claim 1, further comprising preparing latanoprost from said latanoprost acid, wherein in the latanoprost thus obtained the isomeric impurities of trans-latanoprost and 15-epi-latanoprost are not individually more than 0.15%.