Cyclization processes of hydroxyalkenoic acids and products thereof

Patent metadata

Field	Value
Publication number	US-10844050-B2
Application number	US-201816485802-A
Country	US
Kind code	B2
Filing date	Feb 14, 2018
Priority date	Feb 14, 2017
Publication date	Nov 24, 2020
Grant date	Nov 24, 2020

Abstract

The invention provides efficient cyclization processes of hydroxyalkenoic acids and products produced therefrom. The following reactions are claimed: Formula (I), (II), (V) and (VI).

First claim

The invention claimed is:

1. A process for the preparation of a compound of formula (II) comprising the step of:

Reacting a compound of formula (I) in the presence of at least one Pd catalyst and at least one base; R 1 and R 2 are each independently selected from a group consisting of H, straight or branched C 1 -C 15 alkyl, straight or branched C 2 -C 15 alkenyl, straight or branched C 2 -C 15 alkynyl, C 5 -C 12 aryl, C 5 -C 12 heteroaryl; C 3 -C 12 cycloalkyl, C 3 -C 12 heterocycloalkyl; each optionally substituted by at least one OH, amine, amide, halide, straight or branched C 1 -C 15 alkyl, straight or branched C 2 -C 15 alkenyl, straight or branched C 2 -C 15 alkynyl, —O(C 1 -C 8 akyl), —OC(═O)(C 1 -C 8 alkyl), —C(═O)(C 1 -C 8 alkyl), —C(═O)O(C 1 -C 8 alkyl); C 5 -C 12 aryl, C 5 -C 12 heteroaryl, C 3 -C 12 cycloalkyl, C 3 -C 12 heterocycloalkyl; R 3 and R 4 are H; and n is an integer being 1-6.

2. A process for the preparation of a compound of formula (IV) comprising the step of:

reacting a compound of formula (III) in the presence of at least one Pd catalyst and at least one base;
wherein R 2 -R 7 are each independently selected from a group consisting of H, straight or branched C 1 -C 15 alkyl, straight or branched C 2 -C 15 alkenyl, straight or branched C 2 -C 15 alkynyl, C 5 -C 12 aryl, C 5 -C 12 heteroaryl; C 3 -C 12 cycloalkyl, C 3 -C 12 heterocycloalkyl; each optionally substituted by at least one OH, amine, amide, halide, straight or branched C 1 -C 15 alkyl, straight or branched C 2 -C 15 alkenyl, straight or branched C 2 -C 15 alkynyl, —O(C 1 -C 8 akyl), —OC(═O)(C 1 -C 8 alkyl), —C(═O)(C 1 -C 8 alkyl), —C(═O)O(C 1 -C 8 alkyl); C 5 -C 12 aryl, C 5 -C 12 heteroaryl, C 3 -C 12 cycloalkyl, C 3 -C 12 heterocycloalkyl; R 3 and R 4 are H; and n is an integer being 1-6; or R 5 and R 6 or R 6 and R 7 or R 5 and R 7 together with the two carbon atoms they are attached to form a 5 to 15 ring.

3. A process according to claim 1 , wherein R 1 is selected from C 5 -C 12 aryl or C 5 -C 12 heteroaryl, optionally substituted by at least one OH, amine, amide, halide, straight or branched C 1 -C 15 alkyl, straight or branched C 2 -C 15 alkenyl, straight or branched C 2 -C 15 alkynyl, —O(C 1 -C 8 akyl), —OC(═O)(C 1 -C 8 alkyl), —C(═O)(C 1 -C 8 alkyl), —C(═O)O(C 1 -C 8 alkyl); C 5 -C 12 aryl, C 5 -C 12 heteroaryl.

4. A process according to claim 1 , wherein R 1 is selected from straight or branched C 1 -C 15 alkyl, straight or branched C 2 -C 15 alkenyl, straight or branched C 2 -C 5 alkynyl, optionally substituted by at least one OH, amine, amide, halide, —O(C 1 -C 8 akyl), —OC(═O)(C 1 -C 8 alkyl), —C(═O)(C 1 -C 8 alkyl), —C(═O)O(C 1 -C 8 alkyl); C 5 -C 12 aryl, C 5 -C 12 heteroaryl, C 3 -C 12 cycloalkyl, C 3 -C 12 heterocycloalkyl.

5. A process according to claim 1 , wherein R 2 is H.

6. A process according to claim 2 , wherein R 5 and R 6 together with the two carbon atoms they are each attached to form a 5 to 15 membered ring.

7. A process according to claim 2 , wherein R 6 and R 7 together with the two carbon atoms they are each attached to form a 5 to 15 membered ring.

8. A process according to claim 2 , wherein R 5 and R 7 together with the two carbon atoms they are each attached to form a 5 to 15 membered ring.

9. A process according to claim 1 , wherein said at least one Pd catalyst is selected from is selected from Pd(PPh 3 ) 4 , Pd 2 (dba) 3 , Pd(OAc) 2 , PdCl 2 , Pd(acac) 2 and any combinations thereof.

10. A process according to claim 1 , wherein said at least one base is selected from K 2 PO 4 , Cs 2 CO 3 , K 2 CO 3 , NaOAc and any combinations thereof.

11. A process according to claim 1 , being performed in the presence of at least one organic solvent.

12. A process according to claim 1 , being performed in a temperature of between 50° C. to 100° C.

13. A process for the preparation of a compound of formula (VI) comprising the step:

reacting a compound of formula (V) in the presence of at least one Pd catalyst and at least one base; wherein R 2 is selected from a group consisting of H, straight or branched C 1 -C 15 alkyl, straight or branched C 2 -C 15 alkenyl, straight or branched C 2 -C 15 alkynyl, C 5 -C 12 aryl, C 5 -C 12 heteroaryl; C 3 -C 12 cycloalkyl, C 3 -C 12 heterocycloalkyl; each optionally substituted by at least one OH, amine, amide, halide, straight or branched C 1 -C 15 alkyl, straight or branched C 2 -C 15 alkenyl, straight or branched C 2 -C 15 alkynyl, —O(C 1 -C 8 akyl), —OC(═O)(C 1 -C 8 alkyl), —C(═O)(C 1 -C 8 alkyl), —C(═O)O(C 1 -C 8 alkyl); C 5 -C 12 aryl, C 5 -C 12 heteroaryl, C 3 -C 12 cycloalkyl, C 3 -C 12 heterocycloalkyl; R 3 , R 4 and R 5 are H; R 8 is straight or branched C 1 -C 15 alkyl, straight or branched C 2 -C 15 alkenyl, straight or branched C 2 -C 15 alkynyl, each optionally substituted by at least one OH, amine, amide, halide, straight or branched C 1 -C 15 alkyl, straight or branched C 2 -C 15 alkenyl, straight or branched C 2 -C 15 alkynyl, —O(C 1 -C 8 akyl), —OC(═O)(C 1 -C 8 alkyl), —C(═O)(C 1 -C 8 alkyl), —C(═O)O(C 1 -C 8 alkyl); C 5 -C 12 aryl, C 5 -C 12 heteroaryl, C 3 -C 12 cycloalkyl, C 3 -C 12 heterocycloalkyl; and n is an integer being 1-6.

14. A process according to claim 13 , wherein said at least one Pd catalyst is selected from Pd(PPh 3 ) 4 , Pd 2 (dba) 3 , Pd(OAc) 2 , PdCl 2 , Pd(acac) 2 and any combinations thereof.

15. A process according to claim 13 , wherein said at least one base is selected from K 2 PO 4 , Cs 2 CO 3 , K 2 CO 3 , NaOAc and any combinations thereof.

16. A process according to claim 13 , being performed in the presence of at least one organic solvent.

17. A process according to claim 13 , being performed in a temperature of between 50° C. to 100° C.

Assignees

• Yissum Res Dev Co Of Hebrew Univ Jerusalem Ltd

Inventors

• Tsvelikhovsky Dmitry

Classifications

• C07C49/647

  having unsaturation outside the ring · CPC title

• C07D309/32 Primary

  having two double bonds between ring members or between ring members and non-ring members · CPC title

• C07D313/18

  not condensed with other rings · CPC title

• C07D407/04

  directly linked by a ring-member-to-ring-member bond · CPC title

• C07D313/04

  not condensed with other rings · CPC title