Single fluorine substituted methyl ether preparation method

Abstract

The invention provides a process for preparing monofluoromethyl ether, especially fluoromethyl-2,2,2-trifluoro-1-(trifluoromethyl) ethyl ether (sevoflurane), wherein its precursor hexafluoroisopropanol is reacted with trioxymethylene at the presence of fluoro-containing catalyst.

Description

technical field

[0001] The present invention relates to a method for preparing monofluoromethyl ether, especially fluoromethyl-2,2,2-trifluoro-1-(trifluoromethyl)ethyl ether (sevoflurane). technical background

[0002] In recent years it has been discovered that fluorinated ethers are effective inhalational anesthetics. Included among these anesthetics is desflurane (CF 3 CHFOCHF 2 ), isoflurane (CF 3 CHClOCHF 2 ), enflurane (ClFCHCF 2 OCHF 2 ) and sevoflurane ((CF 3 ) 2 CHOCH 2 F). Sevoflurane is a particularly advantageous inhalational anesthetic because of its rapid loss of consciousness and rapid recovery—ideal properties of contemporary inhalational anesthetics. Sevoflurane is delivered to an air-breathing warm-blooded animal through the inhalation route at about 1% to 5% by volume in a mixture with oxygen or in a gaseous mixture containing sufficient oxygen to maintain respiration.

[0003] U.S. Patents US3683092 and US3689571 disclose the use of sevoflurane...

Examples

Embodiment 1

[0025] Add 168g of hexafluoroisopropanol, 11.3g of boron trifluoride etherate complex and 90g of paraformaldehyde into a 250mL single-necked bottle equipped with a magnetic stirring and reflux device, heat and reflux for 5 hours, and after the reaction is completed, 186g is obtained by distillation. According to GC analysis, it contains 90.5% of sevoflurane, and the yield is 84%.

Embodiment 2

[0027] Add 168g of hexafluoroisopropanol, 6.7g of anhydrous aluminum trifluoride, 120mL of chloroform and 90g of paraformaldehyde into a 500mL single-necked bottle with a magnetic stirring and reflux device, heat and reflux for 5 hours, and after the reaction is complete, distill to obtain 164g , containing sevoflurane 88.2% by GC analysis, yield: 72%.

technical field

[0001] The present invention relates to a method for preparing monofluoromethyl ether, especially fluoromethyl-2,2,2-trifluoro-1-(trifluoromethyl)ethyl ether (sevoflurane). technical background

[0002] In recent years it has been discovered that fluorinated ethers are effective inhalational anesthetics. Included among these anesthetics is desflurane (CF 3 CHFOCHF 2 ), isoflurane (CF 3 CHClOCHF 2 ), enflurane (ClFCHCF 2 OCHF 2 ) and sevoflurane ((CF 3 ) 2 CHOCH 2 F). Sevoflurane is a particularly advantageous inhalational anesthetic because of its rapid loss of consciousness and rapid recovery—ideal properties of contemporary inhalational anesthetics. Sevoflurane is delivered to an air-breathing warm-blooded animal through the inhalation route at about 1% to 5% by volume in a mixture with oxygen or in a gaseous mixture containing sufficient oxygen to maintain respiration.

[0003] U.S. Patents US3683092 and US3689571 disclose the use of sevoflurane...

Examples

Embodiment 1

[0025] Add 168g of hexafluoroisopropanol, 11.3g of boron trifluoride etherate complex and 90g of paraformaldehyde into a 250mL single-necked bottle equipped with a magnetic stirring and reflux device, heat and reflux for 5 hours, and after the reaction is completed, 186g is obtained by distillation. According to GC analysis, it contains 90.5% of sevoflurane, and the yield is 84%.

Embodiment 2

[0027] Add 168g of hexafluoroisopropanol, 6.7g of anhydrous aluminum trifluoride, 120mL of chloroform and 90g of paraformaldehyde into a 500mL single-necked bottle with a magnetic stirring and reflux device, heat and reflux for 5 hours, and after the reaction is complete, distill to obtain 164g , containing sevoflurane 88.2% by GC analysis, yield: 72%.

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