# US 2014/0194633 A1 ยท Conversion of 5-(chloromethyl)-2-furaldehyde into 5-methyl-2-furoic acid and derivatives thereof > Agents: this data is available as JSON from the patentgrep API and MCP server โ€” see https://patentgrep.com/llms.txt - Number: US 2014/0194633 A1 - Document ID: US20140194633A1 - Status: Published application - Kind: A1 - Application number: 14/192,828 - Filed: 2014-02-27 - Published: 2014-07-10 - Earliest claimed: 2010-08-19 - Assignees: Xf Technologies B.V. - Inventors: Peter Mikochik; Aviad Cahana - Web page: https://patentgrep.com/patent/US20140194633A1 ## CPC - C07D 307/68: Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen - C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08) ## Abstract The present invention concerns the synthesis of 5-methyl-2-furoic acid, including ester, amide, and thioester derivatives of such from 5-(chloromethyl)-2-furaldehyde (CMF). The molecules so prepared are useful as intermediates for pharmaceutical, food, and fragrance molecules; as well as fuel or fuel additives. ## Claims ### Claim 1 A method for the synthesis of an output consisting of one or more of: an ester of 5-methyl-2-furoic acid, an amide of 5-methyl-2-furoic acid, and a thioester of 5-methyl-2-furoic acid, from a precursor consisting of 5-methyl-furaldehyde with one hydrogen of the 5-methyl group replaced with one of chloride, fluoride, bromide, iodide, p-toluenesulfonate, methanesulfonate, trifluoroacetate, phenoxy, hydroxy, or ammonium, the method comprising: (a) contacting the precursor, a base, an organic solvent, a catalyst, and a reactive nucleophile in a reaction vessel at a temperature of from about 35 degrees C. to about 50 degrees C., such that molecules of the output are produced; (b) separating the molecules of the output by extraction with a hydrophobic solvent, or else by chromatography, distillation, sublimation, or precipitation; wherein the catalyst is one or more of: (1) a N-heterocyclic carbene, (2) a salt of a N-heterocyclic carbene, (3) cyanide, (4) chloride, (5) bromide, (6) iodide, (7) thiazolium, (8) 1,2,4-triazolium, (9) imidazolium, (10) tetrazolium ring system. ### Claim 2 (depends on 1) A method as in claim 1, wherein the output is an ester of 5-methyl-2-furoic acid having an alkoxycarbonyl portion, and wherein the alkoxycarbonyl portion is linear or branched aliphatic chain or a cyclic aliphatic, having at least 1 and not more than 20 carbon atoms. ### Claim 3 (depends on 1) A method as in claim 1, wherein the output is an ester of 5-methyl-2-furoic acid having an aryloxycarbonyl portion, and wherein the aryloxycarbonyl portion is an aromatic ring, having at least 5 and not more than 10 carbon atoms. ### Claim 4 (depends on 1) A method as in claim 1, wherein the reactive nucleophile is an alcohol. ### Claim 5 (depends on 1) A method as in claim 1, wherein the reactive nucleophile is an amine. ### Claim 6 (depends on 1) A method as in claim 1, wherein the reactive nucleophile is a thiol. ### Claim 7 (depends on 1) A method as in claim 1, wherein the hydrophobic solvent comprises a solvent that is immiscible with water. ### Claim 8 A method for the synthesis of an output consisting of one or more of: an ester of 5-methyl-2-furoic acid, an amide of 5-methyl-2-furoic acid, and a thioester of 5-methyl-2-furoic acid, from a precursor consisting of 5-methyl-furaldehyde with one hydrogen of the 5-methyl group replaced with one of chloride, fluoride, bromide, iodide, p-toluenesulfonate, methanesulfonate, trifluoroacetate, phenoxy, hydroxy, or ammonium, the method comprising: (a) contacting the precursor, a base, an organic solvent, a catalyst, and a silanol in a reaction vessel at a temperature of from about โˆ’78 degrees C. to about 150 degrees C., such that molecules of the output are produced; (b) separating the molecules of the output by extraction with a hydrophobic solvent, or else by chromatography, distillation, sublimation, or precipitation; wherein the catalyst is one or more of: (1) a N-heterocyclic carbene, (2) a salt of a N-heterocyclic carbene, (3) cyanide, (4) chloride, (5) bromide, (6) iodide, (7) thiazolium, (8) 1,2,4-triazolium, (9) imidazolium, (10) tetrazolium ring system. ### Claim 9 (depends on 8) A method as in claim 8, wherein the output is an ester of 5-methyl-2-furoic acid having an alkoxycarbonyl portion, and wherein the alkoxycarbonyl portion is linear or branched aliphatic chain or a cyclic aliphatic, having at least 1 and not more than 20 carbon atoms. ### Claim 10 (depends on 8) A method as in claim 8, wherein the output is an ester of 5-methyl-2-furoic acid having an aryloxycarbonyl portion, and wherein the aryloxycarbonyl portion is an aromatic ring, having at least 5 and not more than 10 carbon atoms. ### Claim 11 (depends on 8) A method as in claim 8, wherein the base comprises an inorganic base. ### Claim 12 (depends on 8) A method as in claim 8, wherein the base comprises a nitrogen-containing organic base. ### Claim 13 (depends on 8) A method as in claim 8, wherein the hydrophobic solvent comprises a solvent that is immiscible with water. ### Claim 14 A method for the synthesis of an output consisting of one or more of: an ester of 5-methyl-2-furoic acid, an amide of 5-methyl-2-furoic acid, and a thioester of 5-methyl-2-furoic acid, from a precursor consisting of 5-methyl-furaldehyde with one hydrogen of the 5-methyl group replaced with one of chloride, fluoride, bromide, iodide, p-toluenesulfonate, methanesulfonate, trifluoroacetate, phenoxy, hydroxy, or ammonium, the method comprising: (a) contacting the precursor, a base, an organic solvent, a catalyst, a reactive nucleophile, and tetrabutylammonium bromide or tetrabutylammonium iodide, in a reaction vessel at a temperature of from about โˆ’78 degrees C. to about 150 degrees C., such that molecules of the output are produced; (b) separating the molecules of the output by extraction with a hydrophobic solvent, or else by chromatography, distillation, sublimation, or precipitation; wherein the catalyst is one or more of: (1) a N-heterocyclic carbene, (2) a salt of a N-heterocyclic carbene, (3) cyanide, (4) chloride, (5) bromide, (6) iodide, (7) thiazolium, (8) 1,2,4-triazolium, (9) imidazolium, (10) tetrazolium ring system. ### Claim 15 (depends on 14) A method as in claim 14, wherein the output is an ester of 5-methyl-2-furoic acid having an alkoxycarbonyl portion, and wherein the alkoxycarbonyl portion is linear or branched aliphatic chain or a cyclic aliphatic, having at least 1 and not more than 20 carbon atoms. ### Claim 16 (depends on 14) A method as in claim 14, wherein the output is an ester of 5-methyl-2-furoic acid having an aryloxycarbonyl portion, and wherein the aryloxycarbonyl portion is an aromatic ring, having at least 5 and not more than 10 carbon atoms. ### Claim 17 (depends on 14) A method as in claim 14, wherein the base comprises an inorganic base. ### Claim 18 (depends on 14) A method as in claim 14, wherein the base comprises a nitrogen-containing organic base. ### Claim 19 (depends on 14) A method as in claim 14, wherein the hydrophobic solvent comprises a solvent that is immiscible with water.