# US 4,395,571 A · Process for the preparation of d,1-2-(6-methoxy-2-naphthyl)propionic acid > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 4,395,571 A - Document ID: US4395571A - Status: Granted - Kind: A - Application number: 06/384,445 - Filed: 1982-06-03 - Granted: 1983-07-26 - Earliest claimed: 1982-06-03 - Assignees: Syntex (U.S.A.) Inc. - Inventors: Charles A. Dvorak - Web page: https://patentgrep.com/patent/US4395571A ## CPC - C07C 45/78: Separation; Purification; Stabilisation; Use of additives - C07C 51/29: with halogen-containing compounds which may be formed in situ - C07C: ACYCLIC OR CARBOCYCLIC COMPOUNDS ## Abstract Racemic mixtures of d,1-2-(6-methoxy-2-naphthyl)propanal are resolved by forming a condensation product with N-R-D-glucamine or a salt thereof where R is hydrogen, alkyl of 1 to 36 carbon atoms or cycloalkyl of 3 to 8 carbon atoms, from which a product substantially enriched in d-2-(6-methoxy-2-naphthyl)propanal can be obtained and then can be selectively oxidized to d-2-(6-methoxy-2-naphthyl)propionic acid. ## Claims ### Claim 1 A process for isolating a condensation product of d-2-(6-methoxy-2-naphthyl)propanal comprising crystallizing the condensation product of d-2-(6-methoxy-2-naphthyl)propanal with N-R-D-glucamine or a salt thereof wherein R is hydrogen, alkyl of 1 to 36 carbon atoms or cycloalkyl of 3 to 8 carbon atoms from a mixture containing a first condensation product of d-2-(6-methoxy-2-naphthyl)propanal with N-R-D-glucamine or a salt thereof and a second condensation product of 1-2-(6-methoxy-2-naphthyl)propanal with N-R-D-glucamine or a salt thereof in an inert solvent, the first condensation product being significantly less soluble in the inert solvent than the second condensation product at the crystallization temperature of the first condensation product. ### Claim 2 A process for preparing a condensation product of d-2-(6-methoxy-2-naphthyl)propanal comprising reacting a racemic mixture of d,1-2-(6-methoxy-2-naphthyl)propanal with N-R-D-glucamine or a salt thereof wherein R is hydrogen, alkyl of 1 to 36 carbon atoms or cycloalkyl of 3 to 8 carbon atoms in an inert solvent to form a mixture of a first condensation product of d-2-(6-methoxy-2-naphthyl)propanal with N-R-D-glucamine or a salt thereof and a second condensation product of 1-2-(6-methoxy-2-naphthyl)propanal with N-R-D-glucamine or a salt thereof, the first condensation product being significantly less soluble in the inert solvent than the second condensation product at the crystallization temperature of the first condensation product; and crystallizing the first condensation product from the mixture to yield a product enriched in the first condensation product. ### Claim 3 A process for preparing d-2-(6-methoxy-2-naphthyl)propionic acid comprising crystallizing the condensation product of d-2-(6-methoxy-2-naphthyl)propanal with N-R-D-glucamine or a salt thereof wherein R is hydrogen, alkyl of 1 to 36 carbon atoms or cycloalkyl of 3 to 8 carbon atoms from a mixture containing a first condensation product of d-2-(6-methoxy-2-naphthyl)propanal with N-R-D-glucamine or a salt thereof and a second condensation product of 1-2-(6-methoxy-2-naphthyl)propanal with N-R-D-glucamine or a salt thereof in an inert solvent, the first condensation product being significantly less soluble in the inert solvent than the second condensation product at the crystallization temperature of the first condensation product; hydrolyzing the first condensation product to obtain d-2-(6-methoxy-2-naphthyl)propanal; and oxidizing d-2-(6-methoxy-2-naphthyl)propanal to obtain d-2-(6-methoxy-2-naphthyl)propionic acid. ### Claim 4 A process for preparing d-2-(6-methoxy-2-naphthyl)propionic acid comprising reacting a racemic mixture of d,1-2-(6-methoxy-2-naphthyl)propanal with N-R-D-glucamine or a salt thereof wherein R is hydrogen, alkyl of 1 to 36 carbon atoms or cycloalkyl of 3 to 8 carbon atoms in an inert solvent to form a mixture of a first condensation product of d-2-(6-methoxy-2-naphthyl)propanal with N-R-D-glucamine or a salt thereof and a second condensation product of 1-2-(6-methoxy-2-naphthyl)propanal with N-R-D-glucamine or a salt thereof, the first condensation product being significantly less soluble in the inert solvent than the second condensation product at the crystallization temperature of the first condensation product; crystallizing the first condensation product from the mixture to yield a product enriched in the first condensation product; hydrolyzing the first condensation product to obtain d-2-(6-methoxy-2-naphthyl)propanal; and oxidizing d-2-(6-methoxy-2-naphthyl)propanal to obtain d-2-(6-methoxy-2-naphthyl)propionic acid. ### Claim 5 A process for preparing d-2-(6-methoxy-2-naphthyl)propionic acid comprising hydrolyzing a condensation product of d-2-(6-methoxy-2-naphthyl)propanal with N-R-D-glucamine or a salt thereof wherein R is hydrogen, alkyl of 1 to 36 carbon atoms or cycloalkyl of 3 to 8 carbon atoms to obtain d-2-(6-methoxy-2-naphthyl)propanal; and oxidizing d-2-(6-methoxy-2-naphthyl)propanal to obtain d-2-(6-methoxy-2-naphthyl)propionic acid. ### Claim 6 (depends on 1, 2, 3, 4) The process of claim 1, 2, 3 or 4 including heating the mixture containing the condensation products in the inert solvent to solubilize the condensation products and cooling the heated mixture to subject the mixture to fractional crystallization to obtain a product enriched in the first condensation product. ### Claim 7 (depends on 1, 2, 3, 4) The process of claim 1, 2, 3 or 4 including dissolving the first condensation product in an inert solvent and crystallizing the first condensation product substantially pure therefrom. ### Claim 8 (depends on 1, 2, 3, 4) The process of claim 1, 2, 3 or 4 wherein the salt of N-R-D-glucamine is preformed. ### Claim 9 (depends on 1, 2, 3, 4) The process of claim 1, 2, 3 or 4 wherein the salt of N-R-D-glucamine is formed in situ. ### Claim 10 (depends on 1, 2, 3, 4, 5) The process of claim 1, 2, 3, 4 or 5 wherein R is alkyl of 1 to 18 carbon atoms. ### Claim 11 (depends on 1, 2, 3, 4, 5) The process of claim 1, 2, 3, 4 or 5 wherein R is methyl, n-propyl, n-butyl or n-octyl. ### Claim 12 (depends on 1, 2, 3, 4, 5) The process of claim 1, 2, 3, 4 or 5 wherein R is cycloalkyl of 3 to 8 carbon atoms. ### Claim 13 (depends on 1, 2, 3, 4, 5) The process of claim 1, 2, 3, 4 or 5 wherein R is cyclohexyl. ### Claim 14 (depends on 1, 2, 3, 4, 5) The process of claim 1, 2, 3, 4 or 5 further including recovering a non-racemic mixture of d,1-2-(6-methoxy-2-naphthyl)propanal which remains after removal of the first condensation product from the mixture, racemizing the non-racemic mixture, and recycling the racemized mixture. ### Claim 15 A mixture of the condensation product of d,1-2-(6-methoxy-2-naphthyl)propanal with N-R-D-glucamine or a salt thereof, wherein R is hydrogen, alkyl of 1 to 36 carbon atoms or cycloalkyl of 3 to 8 carbon atoms. ### Claim 16 (depends on 15) The condensation products of claim 15, wherein R is alkyl of 1 to 18 carbon atoms or cyclohexyl. ### Claim 17 A resolving medium comprising a mixture of a first condensation product of d-2-(6-methoxy-2-naphthyl)propanal with N-R-D-glucamine or a salt thereof and a second condensation product of 1-2-(6-methoxy-2-naphthyl)propanal with N-R-D-glucamine or a salt thereof wherein R is hydrogen, alkyl of 1 to 36 carbon atoms or cycloalkyl of 3 to 8 carbon atoms, and a solvent in which the first condensation product is less soluble than the second condensation product to permit fractional crystallization of said condensation products upon the cooling of said medium from an elevated temperature.