4,4,5,5,5-pentafluoropentyl methanesulfonate

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Dissolve 4,4,5,5,5-pentafluoropentanol (8.27 g, 46.42 mmol) in CH2Cl2 (100 mL) and cooled the solution to 0° C. Add triethylamine (20.00 mL, 143.49 mmol), followed by the drop wise addition of methanesulfonyl chloride (4.40 mL, 56.84 mmol). Stir the solution for 45 minutes, then pour into HCl (0.5 N, 100 mL). Wash the organic layer with HCl (0.5 N, 2×100 mL). Dry the organic layer (Na2SO4), filter, and concentrate in vacuo. Recovered 11.48 g (96%) of the desired methanesulfonic acid 4,4,5,5,5-pentafluoro-pentylester as a light yellow oil. 1H NMR (400 MHz, CDCl3): δ 4.31 (t, J=6.0 Hz, 2H), 3.03 (s, 3H), 2.2 (m, 2H), 2.08 (m, 2H). Wash the organic layer with HCl (0.5 N, 2×100 mL) Dry the organic layer (Na2SO4) filter concentrate in vacuo Recovered 11.48 g (96%) of the desired methanesulfonic acid 4,4,5,5,5-pentafluoro-pentylester as a light yellow oil

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Under argon, 15 g (59.2 mmol) of methyl N-(diphenylmethylene)glycinate [described in: WO2010/123792 A1, 2010; pp. 11-13] were initially charged in 127 ml of 1,4-dioxane, the mixture was cooled to 0° C. and 68.1 ml (68.1 mmol) of a 1 N potassium tert-butoxide solution in THF were added. The reaction solution was stirred at 0° C. for 1 h, 21.2 g (78.7 mmol) of 4,4,5,5,5-pentafluoropentyl methanesulphonate [commercially available; additionally described in: H. Kimura et al. Chemistry and Biology 2010, 17, 18-27] were added and the mixture was stirred at 50° C. overnight. The mixture was cooled to RT, 59.2 ml (118.4 mmol) of 2 N hydrochloric acid in diethyl ether and 2.1 ml (118.4 mmol) of water were added and the mixture was stirred vigorously at RT overnight. The reaction mixture was concentrated and the residue was dried under high vacuum. This gave about 17 g of the target compound as a crude mixture which was used without further purification for the next step. Kimura et al. Chemistry and Biology 2010, 17, 18-27] were added the mixture was stirred at 50° C. overnight The mixture was cooled to RT the mixture was stirred vigorously at RT overnight The reaction mixture was concentrated the residue was dried under high vacuum This gave about 17 g of the target compound as a crude mixture which was used without further purification for the next step

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1-Methanesulfonyloxy-4,4,5,5,5-pentafluoropentane (138 g, 538.62 mmol) was dissolved in dimethyl sulfoxide (1000 ml). Sodium cyanide (55.57 g, 1.077 mol) and 18-crown-6 (2.85 g, 10.77 mmol) were added to the solution followed by stirring for 2 hours at 100° C. After cooling to room temperature, water was added to the reaction mixture, which was then extracted twice with ether. The combined organic layers were washed with water and saturated aqueous sodium chloride, and then dried over anhydrous magnesium sulfate. The solvent was distilled off to give 5,5,6,6,6-pentafluorohexanecarbonitrile (108 g, Yield 100%). After cooling to room temperature was then extracted twice with ether The combined organic layers were washed with water and saturated aqueous sodium chloride dried over anhydrous magnesium sulfate The solvent was distilled off

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

Procedure: Sodium iodide (35.1 g, 2.15 mol) was added to a solution of 1-methanesulfonyloxy-4,4,5,5,5-pentafluoropentane (20 g, 0.781 mol) in acetone (200 ml), followed by heating under reflux for 12 hours. After the reaction mixture was filtered, the filtrate was concentrated. Ethyl acetate was added to the residue, which was then filtered again. The filtrate was washed with water and saturated aqueous sodium chloride, and then dried over anhydrous magnesium sulfate. The solvent was distilled off to give 1-iodo-4,4,5,5,5-pentafluoropentane (21.1 g, Yield 93.4%). by heating under reflux for 12 hours After the reaction mixture was filtered the filtrate was concentrated Ethyl acetate was added to the residue, which was then filtered again The filtrate was washed with water and saturated aqueous sodium chloride dried over anhydrous magnesium sulfate The solvent was distilled off

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

Procedure: Trietylamine (46 ml, 0.330 mol) was added to a solution of 4,4,5,5,5-pentafluoropentan-1-ol (25 g, 0.132 mol) in dichloromethane (50 ml). To this solution, methanesulfonyl chloride (20.4 ml, 0.264 mol) was added at 0° C., followed by stirring for 3 hours at room temperature under argon atmosphere. After the reaction was completed, water was added to the reaction mixture, which was then extracted with dichloromethane. The organic layer was washed with 1N aqueous hydrochloric acid, water and saturated aqueous sodium chloride, and then dried over anhydrous magnesium sulfate. After distilling off the solvent, the residue was purified by silica gel flash column chromatography (eluent: hexane/ethyl acetate=1/1) to give 1-methanesulfonyloxy-4,4,5,5,5-pentafluoropentane (34 g, quantitative). was then extracted with dichloromethane The organic layer was washed with 1N aqueous hydrochloric acid, water and saturated aqueous sodium chloride dried over anhydrous magnesium sulfate After distilling off the solvent the residue was purified by silica gel flash column chromatography (eluent: hexane/ethyl acetate=1/1)