Preparation of 3-hydroxy-3,6-dimethylhexahydrobenzofuran-2-one and derivatives thereof

Patent metadata

Field	Value
Publication number	US-10399954-B2
Application number	US-201615759135-A
Country	US
Kind code	B2
Filing date	Sep 12, 2016
Priority date	Sep 11, 2015
Publication date	Sep 3, 2019
Grant date	Sep 3, 2019

Abstract

The present invention relates to the synthesis of intermediate compounds which can be used in the synthesis of mint lactone and related compounds, including 3,6-dimethylhexahydrobenzofuran-2-ones, isomers, and other derivatives.

First claim

The invention claimed is:

1. A method of producing an α-hydroxylactone, comprising the steps of:
(a) forming a cyanohydrin intermediate from a hydroxy-ketone, wherein the hydroxy-ketone is 1-(2-hydroxy-4-methyl-cyclohexyl)ethanone, via cyanohydrin formation, wherein said cyanohydrin intermediate comprises a nitrile; and
(b) hydrolyzing and lactonizing said nitrile of said cyanohydrin intermediate in the presence of an aqueous acid to generate an α-hydroxylactone, wherein said α-hydroxylactone is 3-hydroxy-3,6-dimethylhexahydrobenzofuran-2-one.

2. The method of claim 1 , wherein said hydroxy-ketone is the compound of formula (VI),

and wherein said α-hydroxylactone is the compound of formula IV,

3. The method of claim 1 , wherein said cyanohydrin formation is performed using an aqueous mixture of a cyanide salt in the presence of ammonium chloride.

4. The method of claim 3 , wherein said cyanide salt comprises sodium cyanide or potassium cyanide.

5. The method of claim 1 , wherein the method further comprises the step of forming the hydroxy-ketone by treating isopulegol with O 3 to cleave the double bond, followed by quenching with a suitable quenching agent to generate the 1-(2-hydroxy-4-methyl-cyclohexyl)ethanone.

6. The method of claim 1 , wherein the step of hydrolyzing said cyanohydrin intermediate is performed using a strong aqueous acid, wherein said aqueous acid comprises concentrated hydrochloric acid.

7. The method of claim 2 , further comprising deoxygenating said α-hydroxylactone compound of formula (IV) to yield a compound of formula (VII), a compound of formula (VIII) or a mixture thereof,

8. The method of claim 7 , wherein said α-hydroxylactone compound is deoxygenated via (a) chlorination, followed by (b) reduction with zinc in presence of an acid.

9. The method of claim 2 , further comprising eliminating the hydroxyl group of said α-hydroxylactone of formula (IV) to yield mint lactone, the compound of formula (V),

10. A method of producing mint lactone, the compound of formula (V),

comprising the steps of:
(a) forming a cyanohydrin intermediate from a hydroxy-ketone, wherein the hydroxy-ketone is the compound of formula (VI),

via cyanohydrin formation, wherein said cyanohydrin intermediate comprises a nitrile;
(b) hydrolyzing and lactonizing said nitrile of said cyanohydrin intermediate in the presence of an aqueous acid to generate an α-hydroxylactone, wherein said α-hydroxylactone is the compound of formula IV,

and
(c) eliminating the hydroxyl group of said α-hydroxylactone of formula (IV) to yield the compound of formula (V).

11. The method of claim 10 , further comprising hydrogenating the compound of formula (V) in the presence of a base to obtain a mixture comprising one or more compounds of the following formulas (VII) through (X):

12. The method of claim 11 , wherein said base is introduced to said compound in advance of hydrogenation to promote ring-opening and isomerization.

13. The method of claim 10 , wherein the step of eliminating the hydroxyl group is performed by (a) halogenating said α-hydroxylactone, and eliminating the halogen, or (b) using a strong acid at an elevated temperature.

14. The method of claim 10 , wherein the step of eliminating the hydroxyl group is performed using a strong acid at an elevated temperature, and wherein said strong acid is a phosphoric acid.

15. The method of claim 3 , wherein a phase transfer catalyst is used to facilitate reaction with a nonaqueous phase during said cyanohydrin formation.

16. The method of claim 4 , wherein a phase transfer catalyst is used to facilitate reaction with a nonaqueous phase during said cyanohydrin formation.

17. The method of claim 5 , wherein the suitable quenching agent is sodium bisulfite.

18. The method of claim 7 , wherein said deoxygenation is performed by reacting the compound of formula (IV) with a halogenating agent followed by reduction.

19. The method of claim 8 , wherein the chlorination of step (a) is performed with thionyl chloride or phosphorus trichloride.

20. The method of claim 8 , wherein the acid of the reduction of step (b) is acetic acid.

Assignees

• P2 Science Inc

Inventors

• Foley Patrick
• Yang Yonghua
• Salam Tania

Classifications

• C07C2601/16

  the ring being unsaturated · CPC title

• C07D307/83 Primary

  Oxygen atoms · CPC title

• C07C45/66

  by dehydration · CPC title

• A23L27/2052

  having oxygen or sulfur as the only hetero atoms · CPC title

• A23V2002/00

  Food compositions, function of food ingredients or processes for food or foodstuffs · CPC title