Method for producing hexafluoroisopropanol and fluoromethyl hexafluoroisopropyl ether (sevoflurane)

Patent metadata

Field	Value
Publication number	US-9637435-B1
Application number	US-201615363749-A
Country	US
Kind code	B1
Filing date	Nov 29, 2016
Priority date	Nov 16, 2016
Publication date	May 2, 2017
Grant date	May 2, 2017

Abstract

Disclosed is a method for producing a hexafluoroisopropanol, including the steps of (a) purifying a mixture containing hexafluoroacetone and at least 1,1,1-trifluoro-2,2-dichloroethane as an impurity, thereby obtaining a purified hexafluoroacetone containing 120 ppm or lower of the 1,1,1-trifluoro-2,2-dichloroethane; and (b) bringing hydrogen (H 2 ) into contact with the purified hexafluoroacetone in the presence of a catalyst, thereby hydrogenating the hexafluoroacetone into the hexafluoroisopropanol. It is possible by this method to produce the hexafluoroisopropanol with a short reaction time and a high conversion. Therefore, it is possible to particularly advantageously produce fluoromethyl hexafluoroisopropyl ether (sevoflurane) by using the hexafluoroisopropanol produced by the method.

First claim

The invention claimed is:

1. A method for producing a fluoromethyl hexafluoroisopropyl ether (sevoflurane), comprising the steps of:
(a) purifying a mixture containing hexafluoroacetone and greater than 120 ppm of 1,1,1-trifluoro-2,2-dichloroethane as an impurity, thereby obtaining a purified hexafluoroacetone containing 5-120 ppm of the 1,1,1-trifluoro-2,2-dichloroethane;
(b) bringing hydrogen (H 2 ) into contact with the purified hexafluoroacetone in the presence of a catalyst, thereby hydrogenating the hexafluoroacetone into a hexafluoroisopropanol; and
(c) reacting the hexafluoroisopropanol, formaldehyde, and hydrogen fluoride in the presence of a Lewis acid or a Broensted acid.

2. The method as claimed in claim 1 , wherein the step (a) is conducted by a distillation.

3. The method as claimed in claim 1 , the step (a) comprises the steps of:
(d) bringing water into contact with the mixture containing hexafluoroacetone and greater than 120 ppm of 1,1,1-trifluoro-2,2-dichloroethane as an impurity, thereby converting the hexafluoroacetone contained in the mixture into hexafluoroacetone trihydrate; and
(e) distilling a mixture obtained by the step (d).

4. The method as claimed in claim 3 , wherein the step (e) comprises the steps of:
(f) supplying the mixture obtained by the step (d) into a rectifying column; and
(g) conducting the distillation with a number of theoretical plates of from 2 to 50 and a reflux ratio of 0.5-8.0.

5. The method as claimed in claim 1 , wherein the step (a) comprises the step of:
(h) conducting a quantitative analysis of the hexafluoroacetone by gas chromatography during the purification to see if the content of the 1,1,1-trifluoro-2,2-dichloroethane in the mixture is 5-120 ppm.

6. The method as claimed in claim 1 , wherein the catalyst used in the step (b) is a first catalyst comprising at least one metal selected from the group consisting of palladium, platinum, ruthenium, rhodium, and nickel, or a second catalyst comprising the at least one metal supported on a carrier.

7. The method as claimed in claim 1 , wherein the catalyst used in the step (b) is at least one selected from the group consisting of a third catalyst comprising palladium and ruthenium that are supported on the same carrier, and a fourth catalyst comprising a mixture of a catalyst containing palladium supported on a carrier and a catalyst containing ruthenium supported on a carrier.

8. The method as claimed in claim 1 , wherein the hydrogenation of the step (b) is conducted in the presence of an acid acceptor in a reaction system.

9. The method as claimed in claim 8 , wherein a carbonate or hydrogencarbonate of an alkali metal and a hydroxide of a metal of group 13 of the periodic table are used together as the acid acceptor in the step (b).

10. The method as claimed in claim 1 , wherein the mixture containing hexafluoroacetone and greater than 120 ppm of 1,1,1-trifluoro-2,2-dichloroethane as an impurity to be purified by the step (a) is prepared by a method comprising the steps of:
(i) chlorinating acetone by chlorine (Cl 2 ), thereby obtaining a mixture containing hexachloroacetone; and
(j) fluorinating the hexachloroacetone by bringing hydrogen fluoride into contact with the mixture obtained by the step (i), thereby preparing the mixture containing hexafluoroacetone and greater than 120 ppm of 1,1,1-trifluoro-2,2-dichloroethane as an impurity.

11. The method as claimed in claim 1 , wherein the hexafluoroisopropanol produced by the step (b) is separated by a method comprising the steps of:
(k) separating the catalyst of the step (b) from a reaction mixture obtained by the step (b), thereby obtaining a liquid component; and
(l) distilling the liquid component, thereby separating the hexafluoroisopropanol.

12. A method for producing a fluoromethyl hexafluoroisopropyl ether (sevoflurane), comprising the steps of:
(m) chlorinating acetone by chlorine (Cl 2 ), thereby obtaining a mixture containing hexachloroacetone;
(n) fluorinating the hexachloroacetone by bringing hydrogen fluoride into contact with the mixture obtained by the step (m), thereby preparing a mixture containing hexafluoroacetone and greater than 120 ppm of 1,1,1-trifluoro-2,2-dichloroethane as an impurity;
(o) bringing water into contact with the mixture prepared by the step (n), thereby converting the hexafluoroacetone contained in the mixture into hexafluoroacetone trihydrate;
(p) supplying a mixture obtained by the step (o) into a rectifying column;
(q) conducting a distillation of the mixture obtained by the step (o) in the rectifying column with a number of theoretical plates of from 2 to 50 and a reflux ratio of 0.5-8.0 until the content of the 1,1,1-trifluoro-2,2-dichloroethane in the mixture becomes 5-120 ppm, thereby obtaining a purified hexafluoroacetone trihydrate containing 5-120 ppm of the 1,1,1-trifluoro-2,2-dichloroethane;
(r) bringing hydrogen (H 2 ) into contact with the purified hexafluoroacetone trihydrate in the presence of an acid acceptor and in the presence of at least one catalyst selected from the group consisting of a first catalyst comprising palladium and ruthenium that are supported on the same carrier and a second catalyst comprising a mixture of a catalyst containing palladium supported on a carrier and a catalyst containing ruthenium supported on a carrier, thereby producing a hexafluoroisopropanol; and
(s) reacting the hexafluoroisopropanol obtained by the step (r) with formaldehyde and hydrogen fluoride in the presence of a Lewis acid or a Broensted acid, thereby producing the fluoromethyl hexafluoroisopropyl ether (sevoflurane).

Assignees

• Central Glass Co Ltd

Inventors

• Morino Yuzuru
• Fujii Shigeru
• Nakamichi Toshihiro
• Akiba Shinya
• Takeda Masaaki
• Fujiwara Masaki

Classifications

• G01N30/68

  Flame ionisation detectors · CPC title

• C07C29/145 Primary

  with hydrogen or hydrogen-containing gases · CPC title

• C07C45/82

  by distillation · CPC title

• C07C45/61

  by reactions not involving the formation of >C = O groups · CPC title

• B01J23/462

  Ruthenium · CPC title