# US 9,518,037 B2 · Method for producing N,N-dialkylhomofarnesic acid amide > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 9,518,037 B2 - Document ID: US9518037B2 - Status: Granted - Kind: B2 - Application number: 14/436,795 - Filed: 2013-10-04 - Published: 2016-06-16 - Granted: 2016-12-13 - Earliest claimed: 2012-10-19 - Assignees: Kao Corporation - Applicants: Kao Corporation - Inventors: Kenji Tanino; Takashi Aoki - Web page: https://patentgrep.com/patent/US9518037B2 ## CPC - C07D 307/92: Naphthofurans; Hydrogenated naphthofurans - C07C 231/10: from compounds not provided for in groups C07C231/02 - C07C231/08 - C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08) - C07C: ACYCLIC OR CARBOCYCLIC COMPOUNDS ## Abstract Provided are: a method for producing N,N-dialkylhomofarnesic acid amide, which is a precursor of (±)-3a,6,6,9a-tetramethyldodecahydronaphtho[2.1-b]furan that is useful as a fragrance, at a high recovery rate of a raw material, at a high purity and at a high yield; and a method for producing (±)-3a,6,6,9a-tetramethyldodecahydronaphtho[2.1-b]furan. It is a method for producing N,N-dialkylhomofarnesic acid amide, said method including reacting nerolidol with N,N-dialkylformamide dimethyl acetal under the conditions that the N,N-dialkylformamide dimethyl acetal can be refluxed, wherein the molar ratio of the N,N-dialkylformamide dimethyl acetal to the nerolidol is in a range of 1.5 to 3. ## Claims ### Claim 1 A method for producing N,N-dialkylhomofarnesic acid amide by reacting nerolidol with N,N-dialkylformamide dimethyl acetal under the condition that the N,N-dialkylformamide dimethyl acetal can be refluxed, wherein the molar ratio of the N,N-dialkylformamide dimethyl acetal to the nerolidol is in a range of 1.5 to 3. ### Claim 2 (depends on 1) The method for producing N,N-dialkylhomofarnesic acid amide according to claim 1, wherein the reaction is conducted under the conditions that the N,N-dialkylformamide dimethyl acetal can be refluxed in a case where no organic solvent is contained or an organic solvent is contained in an amount of less than 100 mass % relative to the nerolidol. ### Claim 3 (depends on 2) The method for producing N,N-dialkylhomofarnesic acid amide according to claim 2, wherein the organic solvent is a hydrocarbon. ### Claim 4 (depends on 1) The method for producing N,N-dialkylhomofarnesic acid amide according to claim 1, wherein the molar ratio of the N,N-dialkylformamide dimethyl acetal to the nerolidol is in a range of 2 to 3. ### Claim 5 (depends on 1) The method for producing N,N-dialkylhomofarnesic acid amide according to claim 1, wherein the reflux is conducted using a rectifier. ### Claim 6 (depends on 5) The method for producing N,N-dialkylhomofarnesic acid amide according to claim 5, wherein the number of plates of the rectifier is 3 or more. ### Claim 7 (depends on 5) The method for producing N,N-dialkylhomofarnesic acid amide according to claim 5, wherein the number of plates of the rectifier is 40 or less. ### Claim 8 (depends on 1) The method for producing N,N-dialkylhomofarnesic acid amide according to claim 1, wherein the reflux is conducted under the conditions that the reflux ratio is 3 or more. ### Claim 9 (depends on 1) The method for producing N,N-dialkylhomofarnesic acid amide according to claim 1, wherein the reflux is conducted under the conditions that the reflux ratio is 5 or more and 40 or less. ### Claim 10 (depends on 1) The method for producing N,N-dialkylhomofarnesic acid amide according to claim 1, wherein the condition that the N,N-dialkylformamide dimethyl acetal is refluxed is that the temperature is equal to or higher than the boiling point of the N,N-dialkylformamide dimethyl acetal (III) under the conditions of a pressure of 101 kPa. ### Claim 11 (depends on 1) The method for producing N,N-dialkylhomofarnesic acid amide according to claim 1, wherein the molar ratio of the N,N-dialkylformamide dimethyl acetal to the nerolidol is in a range of 2 to 2.5. ### Claim 12 (depends on 1) The method for producing N,N-dialkylhomofarnesic acid amide according to claim 1, wherein the reflux is conducted under the conditions that the reflux ratio is 8 or more and 15 or less. ### Claim 13 A method for producing (±)-3a,6,6,9a-tetramethyldodecahydronaphtho[2.1-b]furan, comprising Steps 1-4 below: Step 1: reacting nerolidol with N,N-dialkylformamide dimethyl acetal under the conditions that the N,N-dialkylformamide dimethyl acetal can be refluxed to produce N,N-dialkylhomofarnesic acid amide, wherein the molar ratio of the N,N-dialkylformamide dimethyl acetal to the nerolidol is in a range of 1.5 to 3; Step 2: cyclizing the N,N-dialkylhomofarnesic acid amide obtained in Step 1 in the presence of an acidic agent and further hydrolyzing to obtain Sclareolide; Step 3: reducing the Sclareolide obtained in Step 2 so as to obtain Ambroxdiol; and Step 4: dehydrating and cyclizing the Ambroxdiol obtained in Step 3 so as to obtain (±)-3a,6,6,9a-tetramethyldodecahydronaphtho[2.1-b]furan. ### Claim 14 (depends on 13) The method for producing (±)-3a,6,6,9a-tetramethyldodecahydronaphtho[2.1-b]furan according to claim 13, wherein the acidic agent is one or more of Brönsted acid and Lewis acid selected from the group consisting of sulfuric acid, methanesulfonic acid, paratoluenesulfonic acid, chlorosulfonic acid, trifluoromethane sulfonic acid, a metal chloride and a boron trifluoride ether complex. ### Claim 15 (depends on 13) The method for producing (±)-3a,6,6,9a-tetramethyldodecahydronaphtho[2.1-b]furan according to claim 13, wherein the acidic agent is used in an amount of 0.1 to 10 mol times relative to the N,N-dialkylhomofarnesic acid amide (I). ### Claim 16 (depends on 13) The method for producing (±)-3a,6,6,9a-tetramethyldodecahydronaphtho[2.1-b]furan according to claim 13, wherein a solvent is used further in an amount of 1 to 100 mass times relative to the N,N-dialkylhomofarnesic acid amide (I) in Step 2. ### Claim 17 (depends on 16) The method for producing (±)-3a,6,6,9a-tetramethyldodecahydronaphtho[2.1-b]furan according to claim 16, wherein the solvent is a hydrocarbon, a halogenated hydrocarbon, a nitrohydrocarbon, or an ether. ### Claim 18 (depends on 13) The method for producing (±)-3a,6,6,9a-tetramethyldodecahydronaphtho[2.1-b]furan according to claim 13, wherein the cyclization reaction in Step 2 is conducted at a temperature in a range of −70° C. to 100° C. ### Claim 19 (depends on 13) The method for producing (±)-3a,6,6,9a-tetramethyldodecahydronaphtho[2.1-b]furan according to claim 13, wherein the reduction in Step 3 is conducted in the presence of a reducer. ### Claim 20 (depends on 13) The method for producing (±)-3a,6,6,9a-tetramethyldodecahydronaphtho[2.1-b]furan according to claim 13, wherein the dehydration-cyclization in Step 4 is conducted by using a dehydrating agent.