Method for producing N,N-dialkylhomofarnesic acid amide

Patent metadata

Field	Value
Publication number	US-9518037-B2
Application number	US-201314436795-A
Country	US
Kind code	B2
Filing date	Oct 4, 2013
Priority date	Oct 19, 2012
Publication date	Dec 13, 2016
Grant date	Dec 13, 2016

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.

First claim

The invention claimed is:

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.

2. 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.

3. The method for producing N,N-dialkylhomofarnesic acid amide according to claim 2 , wherein the organic solvent is a hydrocarbon.

4. 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.

5. The method for producing N,N-dialkylhomofarnesic acid amide according to claim 1 , wherein the reflux is conducted using a rectifier.

6. 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.

7. 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.

8. 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.

9. 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.

10. 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.

11. 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.

12. 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.

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.

14. 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.

15. 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).

16. 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.

17. 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.

18. 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.

19. 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.

20. 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.

Assignees

• Kao Corp

Inventors

• Tanino Kenji
• Aoki Takashi

Classifications

• C07D307/92 Primary

  Naphthofurans; Hydrogenated naphthofurans · CPC title

• C07C231/10

  from compounds not provided for in groups C07C231/02 - C07C231/08 · CPC title

• C07C233/09

  with carbon atoms of carboxamide groups bound to carbon atoms of an acyclic unsaturated carbon skeleton · CPC title