Methods for preparing fluorinated vinyl ethers

Patent metadata

Field	Value
Publication number	US-9353038-B2
Application number	US-42691909-A
Country	US
Kind code	B2
Filing date	Apr 20, 2009
Priority date	Apr 20, 2009
Publication date	May 31, 2016
Grant date	May 31, 2016

Abstract

A method for preparing a fluorinated vinyl ether compound comprising reacting a fluorinated ether substrate having (i) a hydrogen atom on a carbon atom that is alpha to an etheric oxygen and (ii) a fluorine atom on a carbon atom that is beta to the etheric oxygen, with an organolithium base to provide a reaction product comprising a fluorinated vinyl ether compound.

First claim

What is claimed is:

1. A method for preparing a fluorinated vinyl ether compound, the method comprising:
reacting a fluorinated ether substrate having (i) a hydrogen atom on a carbon atom that is alpha to an etheric oxygen and (ii) a fluorine atom on a carbon atom that is beta to the etheric oxygen, with an organolithium base to provide a reaction product comprising a fluorinated vinyl ether compound,
wherein the reaction is performed in diethoxymethane, and the organolithium base is methyl lithium.

2. The method of claim 1 , wherein the fluorinated ether substrate has the following formula (I):

wherein R 1 is selected from the group consisting of alkyl and haloalkyl;
R 2 is selected from the group consisting of H, F, Cl, alkyl, and haloalkyl; and,
R 3 and R 4 are independently selected from the group consisting of H and F.

3. The method of claim 1 , wherein the fluorinated ether substrate is selected from the group consisting of sevoflurane, sevomethyl ether, chlorosevomethyl ether, difluoromethyl 2,2,2-trifluoroethyl ether, isoflurane, desflurane, chlorodifluoromethyl 2,2,2-trifluoroethyl ether, and bis-(1,2,2,2-tetrafluoroethyl) ether.

4. The method of claim 1 , wherein the fluorinated ether substrate is selected from the group consisting of sevoflurane, sevomethyl ether, chlorosevomethyl ether, desflurane, difluoromethyl 2,2,2-trifluoroethyl ether, and isoflurane.

5. The method of claim 1 , wherein the fluorinated ether substrate has the following formula (II):

wherein R 1 is selected from the group consisting of alkyl and haloalkyl.

6. The method of claim 1 , wherein the halogenated vinyl ether substrate is selected from the group consisting of sevoflurane, sevomethyl ether, and chlorosevomethyl ether.

7. The method of claim 1 , wherein the concentration of methyl lithium in diethoxymethane is between about 0.10 M and about 4.0 M.

8. The method of claim 1 , wherein the organolithium base has a concentration between about 15 molar percent (“mol %”) and about 175 mol % relative to the amount of the fluorinated ether substrate.

9. The method of claim 1 , wherein the organolithium base has a concentration between about 75 mol % and about 125 mol % relative to the amount of the fluorinated ether substrate.

10. The method of claim 1 , further comprising cooling the fluorinated ether substrate to less than or equal to 5 ° C. and adding the organolithium base to the pre-cooled fluorinated ether substrate.

11. The method of claim 1 , further comprising removing the fluorinated vinyl ether compound from the reaction product by applying a vacuum to the reaction product.

12. The method of claim 1 , further comprising isolating the fluorinated vinyl ether from the reaction product by fractional distillation of the reaction product.

13. The method of claim 1 , wherein the fluorinated vinyl ether has a purity of at least 95%.

14. The method of claim 1 , wherein the reaction is performed under an inert atmosphere.

15. A method for preparing fluorinated vinyl ether compounds, the method comprising:
providing a fluorinated ether substrate having a hydrogen atom on a carbon atom that is alpha to an etheric oxygen, and a fluorine atom on a carbon atom that is beta to the etheric oxygen;
cooling the fluorinated ether substrate to less than or equal to 5 ° C.;
adding methyl lithium dissolved in diethoxymethane to the fluorinated ether substrate to provide a reaction mixture; and,
removing a fluorinated vinyl ether compound from the reaction mixture.

16. The method of claim 15 , further comprising stirring the reaction mixture at a temperature that is less than or equal to 5 ° C. before removing the fluorinated vinyl ether compound.

17. The method of claim 15 , wherein removing the fluorinated vinyl ether compound comprises applying a vacuum to the reaction mixture to provide a crude product containing the fluorinated vinyl ether compound and purifying the fluorinated vinyl ether compound by fractional distillation.

18. The method of claim 1 , wherein the organolithium base has a concentration between about 105 mol % and about 125 mol % relative to the amount of the fluorinated ether substrate.

Assignees

• Huang Chialang Grand
• Kudzma Linas V
• Baxter Int
• Baxter Healthcare Sa

Inventors

• Huang Chialang Grand
• Kudzma Linas V

Classifications

• C07C41/24 Primary

  by elimination of halogens, e.g. elimination of HCl · CPC title

• C07C43/17

  containing halogen · CPC title