Water → Sevoflurane

온도

10 °C

In an efficient fume hood, liquid hydrogen fluoride (85.1 g, 4.25 mol) was transferred into a 1 liter Teflon® reaction vessel chilled in a dry ice/acetone cold bath. The vessel was fitted with a dry ice condenser, thermocouple, and addition funnel and a portion of chloromethyl 2,2,2-trifluoro-1-(trifluoromethyl)ethyl ether (80.1 g) was added. A solution of diisopropylethylamine (249.0 g, 1.93 mol) in chloromethyl 2,2,2-trifluoro-1-(trifluoromethyl)ethyl ether (271.0 g) was slowly added while maintaining the internal temperature in the range of -5°to 10° C. After completing the addition, the mixture was transferred to a 2 liter glass boiling flask and the Teflon® vessel was rinsed out with a solution of diisopropylethylamine (307.0 g, 2.38 mol) in chloromethyl 2,2,2-trifluoro-1-(trifluoromethyl)ethyl ether (180.0 g) which was also transferred to the glass flask. An additional 850 g of chloromethyl 2,2,2-trifluoro-1-(trifluoromethyl)ethyl ether was added to the reaction flask to bring the total to 1381.1 g (6.38 mol). This mixture was heated at reflux for 16 hours. After cooling to ambient temperature, water (700 mL) was added to the reaction mixture and, after vigorous shaking, the resultant layers were separated. The lower organic layer was further washed with 700 mL of dilute hydrochloric acid (35 mL of 12 N HCl in 665 mL of water). The organic layer (1259.7 g) was analyzed by NMR and gas chromatography and was shown to consist of 63.6% fluoromethyl 2,2,2-trifluoro-1-(trifluoromethyl)ethyl ether (sevoflurane) and 35.4% recovered chloromethyl 2,2,2-trifluoro-1-(trifluoromethyl)ethyl ether, giving a 95% yield of sevoflurane based on starting material consumed.

1. temperaturechilled in a dry ice/acetone cold bath
2. customThe vessel was fitted with a dry ice condenser
3. additionthermocouple, and addition funnel
4. additionthe addition
5. temperatureThis mixture was heated
6. temperatureat reflux for 16 hours
7. temperatureAfter cooling to ambient temperature
8. customafter vigorous shaking, the resultant layers were separated
9. washThe lower organic layer was further washed with 700 mL of dilute hydrochloric acid (35 mL of 12 N HCl in 665 mL of water)
10. customrecovered chloromethyl 2,2,2-trifluoro-1-(trifluoromethyl)ethyl ether

ORD 기록

ord-7340fa5cac87400bb1091e761f534a93

출처 데이터셋

uspto-grants-1999_03

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US05886239