Method for preparing 3-trifluoromethyl chalcones

Patent metadata

Field	Value
Publication number	US-9834523-B2
Application number	US-201715455691-A
Country	US
Kind code	B2
Filing date	Mar 10, 2017
Priority date	Apr 9, 2008
Publication date	Dec 5, 2017
Grant date	Dec 5, 2017

Abstract

Disclosed is a method for preparing a compound of Formula 1 wherein Q and Z are as defined in the disclosure comprising distilling water from a mixture comprising a compound of Formula 2, a compound of Formula 3, a base comprising at least one compound selected from the group consisting of alkaline earth metal hydroxides of Formula 4 wherein M is Ca, Sr or Ba, alkali metal carbonates of Formula 4a wherein M 1 is Li, Na or K, 1,5-diazabicyclo[4.3.0]non-5-ene and 1,8-diazabicyclo[5.4.0]undec-7-ene, and an aprotic solvent capable of forming a low-boiling azeotrope with water.

Also disclosed is a method for preparing a compound of Formula 2 comprising (1) forming a reaction mixture comprising a Grignard reagent derived from contacting a compound of Formula 5 wherein X is Cl, Br or I with magnesium metal or an alkylmagnesium halide in the presence of an ethereal solvent, and then (2) contacting the reaction mixture with a compound of Formula 6 wherein Y is OR 11 or NR 12 R 13 , and R 11 , R 12 and R 13 are as defined in the disclosure.

Further disclosed is a method for preparing a compound of Formula 7 wherein Q and Z are as defined in the disclosure, using a compound of Formula 1 characterized by preparing the compound of Formula 1 by the method disclosed above or using a compound of Formula 1 prepared by the method disclosed above.

First claim

What is claimed is:

1. A method for preparing a 5-(trifluoromethyl)-4,5-dihydroisoxazole compound of Formula 7

wherein
Z is optionally substituted phenyl; and
Q is phenyl or 1-naphthalenyl, each optionally substituted;

the method comprising
distilling water from a mixture comprising a compound of Formula 2

a compound of Formula 3

a base comprising at least one compound selected from the group consisting of
alkaline earth metal hydroxides of Formula 4
M(OH) 2    4

wherein M is Ca, Sr or Ba,
alkali metal carbonates of Formula 4a
(M 1 ) 2 CO 3    4a

wherein M 1 is Li, Na or K,
1,5-diazabicyclo[4.3.0]non-5-ene and 1,8-diazabicyclo[5.4.0]undec-7-ene, and an aprotic solvent capable of forming a low-boiling azeotrope with water to form a compound of Formula 1

and
contacting said compound of Formula 1 with hydroxylamine and a base to form a 5-(trifluoromethyl)-4,5-dihydroisoxazole compound of Formula 7.

2. The method of claim 1 wherein
Z is

 Q is

R 2a is Cl, F, C 1 -C 2 haloalkyl or C 1 -C 2 haloalkoxy;
R 2b is H, halogen or cyano;
R 2c is H, halogen or CF 3 ;
R 4 is H, C 2 -C 7 alkylcarbonyl or C 2 -C 7 alkoxycarbonyl; and
R 5 is C 1 -C 6 alkyl or C 1 -C 6 haloalkyl, each substituted with one substituent independently selected from hydroxy, C 1 -C 6 alkoxy, C 1 -C 6 alkylthio, C 1 -C 6 alkylsulfinyl, C 1 -C 6 alkylsulfonyl, C 2 -C 7 alkylaminocarbonyl, C 3 -C 9 dialkylaminocarbonyl, C 2 -C 7 haloalkylaminocarbonyl and C 3 -C 9 halodialkylaminocarbonyl.

3. The method of claim 1 wherein
Z is

R 2a is Cl, F, C 1 -C 2 haloalkyl or C 1 -C 2 haloalkoxy;
R 2b is H, halogen or cyano;
R 2c is H, halogen or CF 3 ;
Q is phenyl substituted with two substituents independently selected from R 3 ;
R 3 is independently C 1 -C 6 alkyl or —C(═W)(R 4 )R 5 ;
R 4 is H, C 2 -C 7 alkylcarbonyl or C 2 -C 7 alkoxycarbonyl; and
R 5 is C 1 -C 6 alkyl or C 1 -C 6 haloalkyl, each substituted with one substituent independently selected from hydroxy, C 1 -C 6 alkoxy, C 1 -C 6 alkylthio, C 1 -C 6 alkylsulfinyl, C 1 -C 6 alkylsulfonyl, C 2 -C 7 alkylaminocarbonyl, C 3 -C 9 dialkylaminocarbonyl, C 2 -C 7 haloalkylaminocarbonyl and C 3 -C 9 halodialkylaminocarbonyl.

4. The method of claim 2 wherein
Z is

R 2a is F, Cl, or CF 3 ;
R 2b is H, F, Cl or Br; and
R 2c is H, F, Cl, Br or CF 3 .

5. The method of claim 4 wherein R 2a is Cl; R 2b is F; and R 2c is Cl.

6. The method of claim 4 wherein R 2a , R 2b and R 2c are Cl.

7. The method of claim 4 wherein R 2a is Cl; R 2b is H; and R 2c is Cl.

8. The method of claim 4 wherein R 2a is CF 3 ; R 2b is H; and R 2c is Cl.

9. The method of claim 3 wherein
Z is

R 2a is F, Cl, or CF 3 ;
R 2b is H, Cl or Br; and
R 2c is H, F, Cl, Br or CF 3 .

10. The method of claim 9 wherein R 2a is Cl; R 2b is F; and R 2c is Cl.

11. The method of claim 9 wherein R 2a , R 2b and R 2c are Cl.

12. The method of claim 9 wherein R 2a is Cl; R 2b is H; and R 2c is Cl.

13. The method of claim 9 wherein R 2a is CF 3 ; R 2b is H and R 2c is Cl.

14. A compound of Formula 2:

wherein Z is

R 2a is Cl;
R 2b F; and
R 2c is Cl.

Assignees

• Du Pont

Inventors

• Annis Gary David

Classifications

• C07D261/04 Primary

  having one double bond between ring members or between a ring member and a non-ring member · CPC title

• C07C209/74

  by halogenation, hydrohalogenation, dehalogenation, or dehydrohalogenation · CPC title

• C07D213/40

  Acylated substituent nitrogen atom · CPC title

• C07D249/08

  1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles · CPC title

• C07D413/12

  linked by a chain containing hetero atoms as chain links · CPC title