Process for the synthesis of 7-methoxy-naphthalene-1-carbaldehyde and application in the synthesis of agomelatine

Patent metadata

Field	Value
Publication number	US-9701608-B2
Application number	US-201415101120-A
Country	US
Kind code	B2
Filing date	Dec 4, 2014
Priority date	Dec 5, 2013
Publication date	Jul 11, 2017
Grant date	Jul 11, 2017

Abstract

Process for the industrial synthesis of the compound of formula (I):

First claim

The invention claimed is:

1. A process for the synthesis of a compound of formula (I):

wherein 7-methoxy-naphthalen-2-ol of formula (III):

is used for reaction, the formyl group being introduced at position 1 to yield a compound of formula (IV):

which compound of formula (IV) is subjected to a sulphonylation reaction to yield a compound of formula (V):

wherein R represents —CH 3 , —(CH 2 ) 2 —CH 3 , —CF 3 or tolyl;
which compound of formula (V) undergoes a deoxygenation reaction in the presence of a transition metal and a reducing agent to yield the compound of formula (I), which is isolated in the form of a solid.

2. The process according to claim 1 , wherein R represents —CH 3 or tolyl.

3. The process according to claim 1 , wherein the conversion of the compound of formula (IV) into the compound of formula (V) is carried out by means of the action of a sulphonyl chloride, a sulphonic anhydride or a sulphonimide.

4. The process according to claim 3 , wherein the conversion of the compound of formula (IV) into the compound of formula (V) is carried out by means of the action of a sulphonyl chloride.

5. The process according to claim 1 , wherein, in the conversion of the compound of formula (V) into the compound of formula (I), the transition metal is nickel, palladium or platinum.

6. The process according to claim 1 , wherein, in the conversion of the compound of formula (V) into the compound of formula (I), the transition metal is a palladium salt.

7. The process according to claim 1 , wherein the conversion of the compound of formula (V) into the compound of formula (I) is carried out in dimethylformamide, dioxane, tetrahydrofuran or toluene.

8. The process according to claim 7 , wherein the conversion of the compound of formula (V) into the compound of formula (I) is carried out in dimethylformamide.

9. The process according to claim 1 , wherein the conversion of the compound of formula (V) into the compound of formula (I) is carried out between 25° C. and 110° C.

10. The process according to claim 9 , wherein the conversion of the compound of formula (V) into the compound of formula (I) is carried out between 40° C. and 95° C.

11. The process according to claim 1 , wherein, in the conversion of the compound of formula (V) into the compound of formula (I), the reducing agent is dihydrogen.

12. The process according to claim 11 , wherein the dihydrogen is obtained by decomposition of an ammonium formate.

13. The process according to claim 1 , wherein the conversion of the compound of formula (V) into the compound of formula (I) is carried out in the presence of palladium and dihydrogen.

14. The process according to claim 1 , wherein the conversion of the compound of formula (V) into the compound of formula (I) is carried out in the presence of (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphane) or 1,3-bis(diphenylphosphino)propane.

15. A compound of formula (V):

wherein R represents —(CH 2 ) 2 —CH 3 , —CF 3 or tolyl.

16. A process for the synthesis of agomelatine employing a compound of formula (V)

wherein R represents —CH 3 , —(CH 2 ) 2 —CH 3 , —CF 3 or tolyl.

17. The compound according to claim 15 , which is selected from the following compounds:
1-formyl-7-methoxynaphthalen-2-yl 4-methylbenzenesulphonate and
1-formyl-7-methoxynaphthalen-2-yl methanesulphonate.

18. A process for the synthesis of the compound of formula (I):

employing a compound of formula (V)

wherein R represents —CH 3 , —(CH 2 ) 2 —CH 3 , —CF 3 or tolyl.

19. The process according to claim 18 , wherein the process further comprises subjecting the compound of formula (I) to a series of reactions to provide agomelatine.

20. A process for the synthesis of a compound of formula (I)

employing a compound of formula (III):

21. The process according to claim 20 , wherein the process further comprises subjecting the compound of formula (I) to a series of reactions to provide agomelatine.

22. The process according to claim 16 , wherein methoxy-naphthalen-2-ol of formula (III):

is used for reaction, and a formyl group is introduced at position 1 to yield a compound of formula (IV):

which compound of formula (IV) is subjected to a sulphonylation reaction to yield the compound of formula (V), which compound of formula (V) is subjected to a series of reactions to provide agomelatine.

Assignees

• Servier Lab
• Les Laboratories Servier

Inventors

• Briere Jean-Françoís
• Lebeuf Raphaël
• Levacher Vincent
• Hardouin Christophe
• Lecouve Jean-Pierre

Classifications

• C07C309/73

  to carbon atoms of non-condensed six-membered aromatic rings · CPC title

• C07C309/66

  Methanesulfonates · CPC title

• C07C303/28

  by reaction of hydroxy compounds with sulfonic acids or derivatives thereof · CPC title

• C07C47/575

  containing ether groups, [IMAGE cpc-sch-C07C-0958.gif] groups,[IMAGE cpc-sch-C07C-0959.gif] groups, or[IMAGE cpc-sch-C07C-0960.gif] groups · CPC title

• C07C45/86

  Use of additives, e.g. for stabilisation · CPC title