2-chloro-2-(difluoromethoxy)-1,1,1-trifluoroethane

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Each dog fasting one whole day and night (weighing about 10 kg) received atropine sulfate as a pre-anesthesia drug intravenously followed by intravenous sodium thiopental to effect the anesthesia. An intratracheal tube was inserted and fixed. A gas mixture of nitrous oxide and oxygen was introduced. Using an isoflurane vaporizer the isoflurane was introduced. The concentration of the isoflurane was increased gradually from 0.5%, whereby maintaining the anesthesia. An intratracheal tube was inserted was introduced was introduced maintaining the anesthesia

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Each dog fasting one whole day and night (weighing about 10 kg) received atropine sulfate as a pre-anesthesia drug intravenously followed by intravenous sodium thiopental to effect the anesthesia. An intratracheal tube was inserted and fixed. A gas mixture of nitrous oxide and oxygen was introduced. Using an isoflurane vaporizer the isoflurane was introduced. The concentration of the isoflurane was increased gradually from 0.5%, whereby maintaining the anesthesia. An intratracheal tube was inserted was introduced was introduced maintaining the anesthesia

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Each dog fasting one whole day and night (weighing about 10 kg) received atropine sulfate as a pre-anesthesia drug intravenously followed by intravenous sodium thiopental to effect the anesthesia. An intratracheal tube was inserted and fixed. A gas mixture of nitrous oxide and oxygen was introduced. Using an isoflurane vaporizer the isoflurane was introduced. The concentration of the isoflurane was increased gradually from 0.5%, whereby maintaining the anesthesia. An intratracheal tube was inserted was introduced was introduced maintaining the anesthesia

Conditions: temp:195.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 12.9 g of isoflurane (FORANE® isoflurane commercially available from Anaquest Division of BOC, Inc. in Madison, Wis.) were combined with 5.5 g of potassium fluoride and 20 ml of diethylglycol and the mixture was heated with stirring for 10 hours in a glass pressure vessel at 195° C. The heated mixture was washed with ice water and the organic layer was subjected to gas chromatography, which showed the presence of the compound CHF2OCHFCF3 (29% yield). the mixture was heated The heated mixture was washed with ice water

Conditions: temp:195.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 12.9 g of isoflurane (FORANE® isoflurane commercially available from Anaquest Division of BOC, Inc. in Madison, Wis.) were combined with 5.5 g of potassium fluoride and 20 ml of diethylglycol and the mixture was heated with stirring for 10 hours in a glass pressure vessel at 195° C. The heated mixture was washed with ice water and the organic layer was subjected to gas chromatography, which showed the presence of the compound CHF2OCHFCF3 (29% yield). the mixture was heated The heated mixture was washed with ice water

Conditions: temp:283.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 1 liter autoclave (316SS, Parr) was charged with 399 g (2.2 moles) isoflurane and 84 g (2.0 moles) of sodium fluoride. The reaction mass was heated to 283° C. without stirring. After 24 hours at 283° C., the pressure was 1160 psi. The autoclave was then cooled to ca. 10° C. and the crude products (228 g) transferred by pouring into a distillation flask. Distillation through a four foot vacuum jacketed column packed with glass beads gave 73.4 g CHF2OCHFCF3. The material remaining in the distillation flask was found by GC analysis to be 99.6% isoflurane. Based on the materials isolated the percent conversion was 20% (31% yield). Details of the distillation are given below. The autoclave was then cooled to ca. 10° C. by pouring into a distillation flask Distillation through a four foot vacuum

Conditions: temp:283.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 1 liter autoclave (316SS, Parr) was charged with 399 g (2.2 moles) isoflurane and 84 g (2.0 moles) of sodium fluoride. The reaction mass was heated to 283° C. without stirring. After 24 hours at 283° C., the pressure was 1160 psi. The autoclave was then cooled to ca. 10° C. and the crude products (228 g) transferred by pouring into a distillation flask. Distillation through a four foot vacuum jacketed column packed with glass beads gave 73.4 g CHF2OCHFCF3. The material remaining in the distillation flask was found by GC analysis to be 99.6% isoflurane. Based on the materials isolated the percent conversion was 20% (31% yield). Details of the distillation are given below. The autoclave was then cooled to ca. 10° C. by pouring into a distillation flask Distillation through a four foot vacuum

Conditions: temp:283.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 1 liter autoclave (316SS, Parr) was charged with 399 g (2.2 moles) isoflurane and 84 g (2.0 moles) of sodium fluoride. The reaction mass was heated to 283° C. without stirring. After 24 hours at 283° C., the pressure was 1160 psi. The autoclave was then cooled to ca. 10° C. and the crude products (228 g) transferred by pouring into a distillation flask. Distillation through a four foot vacuum jacketed column packed with glass beads gave 73.4 g CHF2OCHFCF3. The material remaining in the distillation flask was found by GC analysis to be 99.6% isoflurane. Based on the materials isolated the percent conversion was 20% (31% yield). Details of the distillation are given below. The autoclave was then cooled to ca. 10° C. by pouring into a distillation flask Distillation through a four foot vacuum

Conditions: temp:278.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 1 liter autoclave (316SS, Parr) was charged with 171 g (0.93 moles) isoflurane and 116 g (2.0 moles) potassium fluoride. The reaction mass was heated with stirring to 278° C. After 18 hours at 278° C., the pressure was 500 psi. The autoclave was then cooled to room temperature for transfer to the laboratory. Products were then distilled into a dry ice cooled trap by heating the autoclave on a hot plate. The trap contents (134 g) were distilled through a four foot vacuum jacketed column packed with glass beads to give 20.8 g CHF2OCHFCF3 (bp 23.5° C.). The material remaining in the distillation flask (104.0 g) was 98% isoflurane. Based on the materials isolated, the percent conversion was 13% (33% yield). Details of the distillation are given below. The reaction mass was heated The autoclave was then cooled to room temperature for transfer to the laboratory Products were then distilled into a dry ice cooled trap by heating the autoclave on a hot plate The trap contents (134 g) were distilled through a four foot vacuum

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 6-ft×2-inch tube was charged with chromia catalyst and isoflurane and 5 mole equivalents of HF were introduced in vapor form at a pressure of 150 psig. The by-product HCl, desflurane, unreacted isoflurane and unreacted HF that exited the tube were collected and distilled at 150 psig to remove HCl. After HCl was removed, the reaction mixture was heated at total reflux. At a pressure of 150 psig, the material collected overhead at 82° C. was the desflurane/hydrogen fluoride azeotrope. The composition of the azeotrope, after analysis was determined to be 85% desflurane and 15% HF, by weight. The table below shows the boiling point and composition of the azeotrope at different pressures. were introduced in vapor form at a pressure of 150 psig were collected distilled at 150 psig to remove HCl After HCl was removed the reaction mixture was heated at total reflux At a pressure of 150 psig, the material collected overhead at 82° C.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: It has been found that fractional distillation of a crude reaction mixture obtained in the manufacture of desflurane, for example, by reacting hydrogen fluoride with isoflurane over a bed of chromia catalyst, results in the removal of desflurane in the form of a desflurane/hydrogen fluoride azeotrope that boils below the boiling point of hydrogen fluoride. It has been found that fractional distillation of a crude reaction mixture

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The mice were anesthetized with Isoflurane, and then were given an intramuscular injection of 0.1 mL solution of ketamine (50 mg/kg) and xylazine (10 mg/kg). Approximately 10 minutes after the i.m. injection (after the mice could not turn over when placed on their backs), the mice were treated with 12.3 μL of a 10 mg/mL fluasterone/ethanol:limonene:isopropyl myristate solution to give a dose of 5 mg/kg. The mice were anesthetized and on their backs for approximately 30 minutes after application of fluasterone:ethanol:limonene:isopropyl myristate solution. One hour after the application of fluasterone solution, 2 μg of TPA dissolved in 0.2 mL of acetone was applied to the shaved area on the back of each mouse. Approximately 10 minutes