Processes for the preparation of ortho-allylated hydroxy aryl compounds

Patent metadata

Field	Value
Publication number	US-11512034-B2
Application number	US-202117303462-A
Country	US
Kind code	B2
Filing date	May 28, 2021
Priority date	May 29, 2020
Publication date	Nov 29, 2022
Grant date	Nov 29, 2022

Abstract

The present application describes process for preparing an ortho-allylated hydroxy aryl compounds such as compounds of Formula (I) by reacting an allylic alcohol with a hydroxy aryl compound in the presence of aluminum compound selected from alumina and aluminum alkoxides and in a non-protic solvent wherein at least one carbon atom ortho to the hydroxy group in the hydroxy aryl compound is unsubstituted. The present application also includes compounds of Formula (I).

First claim

The invention claimed is:

1. A process for preparing a compound of Formula (I-A)

comprising:
reacting a compound of Formula (II)

with a compound of Formula (III)

in the presence of acidic alumina and in a non-protic solvent to form the compound of Formula (I-A),
wherein
R 1 is C 1-12 alkyl;
R 2 is H;
R 3 is selected from H and CH 3 ;
R 4 is selected from H and CH 3 ; and
R 5 is selected from

wherein

 represents a point of covalent attachment.

2. The process of claim 1 , wherein the a non-protic solvent is selected from hexane, hexanes, heptane, heptanes, cyclohexane, petroleum ether, octane, diglyme, toluene, xylenes, benzene, chloroform, fluorinated alkanes, dichloromethane (DCM), 1,2-dichloroethane (DCE), ethyl acetate, carbon tetrachloride, tetrahydrofuran (THF), diethyl ether, diisopropyl ether, isooctane, methyl ethyl ketone, acetone, dimethyl sulfoxide, dimethylformamide, methyl tert-butyl ether, trichloroethane, n-butyl acetate, chlorobenzene acetonitrile, and trifluorotoluene, and mixtures thereof.

3. The process of claim 1 , wherein the process further comprises a dehydrating agent and/or an acid.

4. The process of claim 1 , wherein the process provides the compound of Formula (I-A) as the as the major product of the process and in a yield of greater than about 50%.

5. The process of claim 1 , wherein the forming of the compound of Formula (I-A) further comprises mixing the compound of Formula (II), the compound of Formula (III) and the acidic alumina in the non-protic solvent with the addition of the acidic alumina in the amount of about 1 g to about 3 g per 1 mmol of the compound of Formula II).

6. The process of claim 1 , wherein R 1 is C 1-6 alkyl.

7. The process of claim 1 , wherein R 1 is C 1-4 alkyl.

8. The process of claim 1 , wherein R 1 is C 1 alkyl.

9. The process of claim 1 , wherein R 1 is C 2 alkyl.

10. The process of claim 1 , wherein R 1 is C 3 alkyl.

11. The process of claim 1 , wherein R 1 is C 4 alkyl.

12. The process of claim 1 , wherein R 1 is C5alkyl.

13. The process of claim 1 , wherein R 3 is H.

14. The process of claim 1 , wherein R 4 is CH 3 .

15. The process of claim 1 , wherein the compound of Formula (I-A) is a compound selected from:

16. The process of claim 1 , wherein the forming of the compound of Formula I-A comprises reacting about 1.1 to about 5 molar equivalents of the compound of Formula II relative to the compound of Formula III.

17. The process of claim 1 , wherein the forming of the compound of Formula (I-A) comprises reacting the compound of Formula (II) with the compound of Formula (III) and under heating in the presence of the acid alumina and the non-protic solvent.

18. The process of claim 17 , wherein the compound of Formula (II) and the compound of Formula (III) are present in a (II):(III) ratio of about 5:1.1 to about 1:5.

19. The process of claim 1 , wherein the reacting of the compound of Formula (II) with the compound of Formula (III) in the presence of acidic alumina and in a non-protic solvent provides a reaction mixture and the process further comprises separating the compound of Formula (I-A) from by one or more of a chromatography step, a distillation step or a crystallization step.

20. The process of claim 1 , wherein non-protic solvent selected from hexane, heptane, cyclohexane, toluene, chloroform, dichloromethane (DCM), 1,2-dichloroethane (DCE), diethyl ether, methyl tert-butyl ether, and trifluorotoluene, and mixtures thereof.

21. the process of claim 1 , wherein the acid alumina is in an amount of about 2.16 to about 147 molar equivalents with respect to the compound (II).

Assignees

• Univ Mcmaster

Inventors

• Magolan Jakob
• Jentsch Nicholas
• Zhang Xiong
• Piotrowski Mathew

Classifications

• C07D311/32

  2,3-Dihydro derivatives, e.g. flavanones · CPC title

• C07C201/12

  by reactions not involving the formation of nitro groups · CPC title

• B01J2231/4205

  C-C cross-coupling, e.g. metal catalyzed or Friedel-Crafts type · CPC title

• B01J21/04

  Alumina · CPC title

• C07D311/30

  not hydrogenated in the hetero ring, e.g. flavones · CPC title