Baxter International Inc.

Baxter Healthcare Sa

Anaquest, Inc.

Ohmeda Pharmaceutical Products Division Inc.

Leonid A Rozov

Ralph A Lessor

Linas V Kudzma

Gerald G Vernice

Chialang Huang

Ronald Bell

Hong-Chang Lee

Yongxian Zeng

Keith Ramig

Donald F Halpern

Fernando Quiroz

Linas Kudzma

A method for cleaning a distilling column includes providing a distilling column including a packing containing nickel and adding hydrochloric acid to the distilling column to wash at least a portion of the packing, thereby cleaning the distilling column.

Methods for cleaning distilling columns

The present invention provides a method for forming sevoflurane comprising (i) combining chlorosevo ether, a nucleophilic fluoride reagent, and a solvent comprising sevoflurane to form an initial reaction mixture and (ii) reacting the initial reaction mixture to form additional sevoflurane relative to the amount of sevoflurane present in the initial reaction mixture. The present disclosure is also directed to a method for forming sevoflurane, comprising: initiating a reaction between chlorosevo ether and a nucleophilic fluoride reagent in an initial reaction mixture further comprising a solvent comprising sevoflurane, thereby forming additional sevoflurane relative to the amount of sevoflurane present in the initial reaction mixture.

Process for the manufacturing of sevoflurane

Provided is a process of obtaining 1,1,1,3,3,3-hexafluoro-2-propanol ('HFIP') from a composition comprising an HFIP hydrolyzable precursor. The HFIP hydrolyzable precursor is a compound, other than sevoflurane itself, that has an intact 1,1,1,3,3,3-hexafluoroisopropoxy moiety[(CF)CHO&#x2014;], and contains one or more moieties susceptible to acidic hydrolysis, such that HFIP is released upon such treatment. The process is useful, among other things, for recovering HFIP from waste streams associated with the synthesis of the inhalation anesthetic, fluoromethyl 2,2,2-trifluoro-1-(trifluoromethyl)ethyl ether ('sevoflurane'). The process includes heating the composition with a strong protic acid to a temperature effective to hydrolyze at least some of the HFIP hydrolyzable precursor to HFIP, and then isolating the HFIP from the heated composition.

Process for recovery of 1,1,1,3,3,3-hexafluoroisopropanol from the waste stream of sevoflurane synthesis

Provided is a method for the preparation of desflurane wherein isoflurane is reacted with 0.7-1.2 mol. % of antimony pentachloride and 1.3-2.2 molar equivalents of hydrogen fluoride. Typically, the method is conducted by addition of hydrogen fluoride to a mixture of isoflurane and antimony pentachloride. After the addition of hydrogen fluoride is completed, the reaction is preferably maintained at temperatures of about 9-18&deg; C. for about 6 to 7 hours, before being quenched.

Preparation of desflurane

A method of preparing fluoromethyl 2,2,2-trifluoro-1-(trifluoromethyl)ethyl ether (sevoflurane) and structurally related monofluoromethyl ethers in which the monochloromethyl ether precursor thereof is reacted with a sterically hindered tertiary amine hydrofluoride salt.

Method of preparing monofluoromethyl ethers

An improved process for the production of isoflurane is disclosed. Isoflurane is formed by the exhaustive chlorination of 2,2,2-trifluoroethyl difluoromethyl ether with chlorine gas. The reaction mixture, preferably without purification or refining, is treated with UV light in the presence of isopropanol to reduce 1,1-dichloro-2,2,2-trifluoroethyl difluoromethyl ether, the other major component thereof, to isoflurane. Isoflurane is thereby obtained in yields of at least 80%.

Preparation of isoflurane

A process for the preparation of highly purified optical isomers of desflurane, i.e. 2-(difluoromethoxy)-1,1,1,2-tetrafluoroethane, is described wherein the highly purified opposite optical isomer of iso-flurane is reacted with bromine trifluoride in the cold, preferably in the presence of a solvent. A preferred solvent is bromine. The highly purified positive isomer of desflurane is advantageous over the negative isomer or the racemate.

Preparation of purified optical isomers of desflurane

An improved preparation of desflurane, 1,2,2,2-tetrafluoroethyl difluoromethyl ether utilizing hexafluoropropene epoxide as a starting material. Hexafluoropropene epoxide is advantageous in that it is relatively inexpensive and is environmentally acceptable.

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Fair Lawn, NJ, United States of America

Leonid A Rozov