1-chloro-4-(trifluoromethoxy)benzene

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

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

Procedure: Chlorine and p-nitrotrifluoromethoxybenzene (10.7 parts) were fed simultaneously at a molar ratio of 3:1, Cl2 : organic reactant, into a vapor phase reactor maintained at 300° to 320° C. over a 30 minute period to yield 8.2 parts of p-chlorotrifluoromethoxybenzene (83% yield). The structure of the product was confirmed by gas chromatographic-mass spectrum and F19 nuclear magnetic resonance analysis. organic reactant, into a vapor phase reactor maintained at 300° to 320° C. over a 30 minute period

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

Procedure: Chlorine and p-nitrotrifluoromethoxybenzene (10.7 parts) were fed simultaneously at a molar ratio of 3:1, Cl2 : organic reactant, into a vapor phase reactor maintained at 300° to 320° C. over a 30 minute period to yield 8.2 parts of p-chlorotrifluoromethoxybenzene (83% yield). The structure of the product was confirmed by gas chromatographic-mass spectrum and F19 nuclear magnetic resonance analysis. organic reactant, into a vapor phase reactor maintained at 300° to 320° C. over a 30 minute period

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

Procedure: To a solution of the 4-chloro(trifluoromethoxy)benzene (2.0 g, 10.18 mmol) in dry tetrahydrofuran (THF, 30 ml) at −78° C., was added ethylenediaminetetraacetic acid (EDTA, 1.24 g, 10.7 mmol) followed by a 1.3 M solution of sec-butyllithium in cyclohexane (7.63 ml, 10.7 mmol) and the reaction stirred for 2 hours under nitrogen. To this reaction mixture at −78° C., was then added dropwise the preformed dimethoxyfluoroborane mixture. The reaction was stirred at −78° C. for 30 minutes, warmed to room temperature for 30 minutes, and then quenched with water (10 ml). The reaction mixture was extracted with diethyl ether (4×50 ml). The combined organic extracts were dried over MgSO4 and concentrated in vacuo. To purify, the residue was dissolved in diethyl ether (10 ml) and washed with an aqueous solution of 10% NaOH (50 ml). The aqueous layer was acidified and extracted with ethyl acetate (3×40 ml). The combined ethyl acetate extracts were dried over MgSO4 and concentrated in vacuo to afford a mixture of the title compound and its corresponding regioisomer as a white solid (0.862 g). The reaction was stirred at −78° C. for 30 minutes quenched with water (10 ml) The reaction mixture was extracted with diethyl ether (4×50 ml) The combined organic extracts were dried over MgSO4 concentrated in vacuo To purify the residue was dissolved in diethyl ether (10 ml) washed with an aqueous solution of 10% NaOH (50 ml) extracted with ethyl acetate (3×40 ml) The combined ethyl acetate extracts were dried over MgSO4 concentrated in vacuo to afford

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

Procedure: Chlorine and p-nitrotrifluoromethoxybenzene (10.7 parts) were fed simultaneously at a molar ratio of 3:1, Cl2 : organic reactant, into a vapor phase reactor maintained at 300° to 320° C. over a 30 minute period to yield 8.2 parts of p-chlorotrifluoromethoxybenzene (83% yield). The structure of the product was confirmed by gas chromatographic-mass spectrum and F19 nuclear magnetic resonance analysis. organic reactant, into a vapor phase reactor maintained at 300° to 320° C. over a 30 minute period

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

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

Procedure: Chlorine and p-nitrotrifluoromethoxybenzene (10.7 parts) were fed simultaneously at a molar ratio of 3:1, Cl2 :organic reactant, into a vapor phase reactor maintained at 300° C. to 320° C. over a 30 minute period to yield 8.2 parts of p-chlorotrifluoromethoxybenzene (83% yield). The structure of the product was confirmed by gas chromatographic--mass spectrum and F19 nuclear magnetic resonance analysis. organic reactant, into a vapor phase reactor maintained at 300° C. to 320° C. over a 30 minute period

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

Procedure: A 1.6 M solution of butyllithium in hexanes (26.5 mmol, 16.5 mL) was added to a 0° C. solution of diisopropylamine (2.65 g, 26.5 mmol) in tetrahydrofuran (50 mL). The solution was cooled to −100° C., and 1-chloro-4-(trifluoromethoxy)benzene (Matrix) (5.0 g, 26.5 mmol) was added. After 2 h at −100° C., the mixture was poured onto an excess of freshly crushed dry ice. After evaporation of the volatiles, the residue was dissolved in a 1 M aqueous solution (50 mL) of sodium hydroxide, washed with diethyl ether (2×15 mL), and acidified to pH 1 by the addition of concentrated hydrochloric acid (7 mL). The aqueous layers were extracted with diethyl ether (3×30 mL). The combined organic extracts were dried (MgSO4), filtered and concentrated to afford the title product. 1H NMR (300 MHz, DMSO-d6) δ ppm 7.54 (dd, J=8.8, 1.0 Hz, 1H) 7.78 (dd, J=8.8, 2.7 Hz, 1H) 7.92 (d, J=2.7 Hz, 1H). After evaporation of the volatiles the residue was dissolved in a 1 M aqueous solution (50 mL) of sodium hydroxide washed with diethyl ether (2×15 mL) acidified to pH 1 by the addition of concentrated hydrochloric acid (7 mL) The aqueous layers were extracted with diethyl ether (3×30 mL) The combined organic extracts were dried (MgSO4) filtered concentrated

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

Procedure: Chlorine and p-nitrotrifluoromethoxybenzene (10.7 parts) were fed simultaneously at a molar ratio of 3:1, Cl2 :organic reactant, into a vapor phase reactor maintained at 300° to 320° C. over a 30 minute period to yield 8.2 parts of p-chlorotrifluoromethoxybenzene (83% yield). The structure of the product was confirmed by gas chromatographic-mass spectrum and F19 nuclear magnetic resonance analysis. organic reactant, into a vapor phase reactor maintained at 300° to 320° C. over a 30 minute period

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

Procedure: Under an atmosphere of nitrogen, a mixture of 6.5 g of bis-triphenylphosphine-nickel dichloride, 5 g of triphenylphosphine and 120 ml of MEK was stirred at room temperature for 10 minutes. 1.9 g of activated zinc powder were then added, and the reaction mixture was stirred at 70° C. for 30 minutes. Following this, the mixture was allowed to cool to 25° C., and 93.25 g of 1-chloro-4-trifluoromethoxybenzene were added dropwise. The mixture was stirred for 10 minutes, 24 g of sodium cyanide were added, and the reaction mixture was stirred at from 65 to 70° C. for 20 h. The conversion was then approximately 75% (GC). After cooling to room temperature, the mixture was filtered, the solid filter residue was washed 2× with 50 ml of MEK and the combined organic phases were concentrated under reduced pressure. Vacuum distillation gave 58.5 g (66% of theory) of 4-trifluoromethoxybenzonitrile as a colourless liquid (boiling point at 120 mbar: 80° C.). 2.6% of coupling products had formed. the reaction mixture was stirred at 70° C. for 30 minutes to cool to 25° C. The mixture was stirred for 10 minutes the reaction mixture was stirred at from 65 to 70° C. for 20 h After cooling to room temperature the mixture was filtered the solid filter residue was washed 2× with 50 ml of MEK the combined organic phases were concentrated under reduced pressure Vacuum distillation

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

Procedure: To a solution of the 4-chloro(trifluoromethoxy)benzene (2.0 g, 10.18 mmol) in dry tetrahydrofuran (THF, 30 ml) at −78° C., was added ethylenediaminetetraacetic acid (EDTA, 1.24 g, 10.7 mmol) followed by a 1.3 M solution of sec-butyllithium in cyclohexane (7.63 ml, 10.7 mmol) and the reaction stirred for 2 hours under nitrogen. To this reaction mixture at −78° C., was then added dropwise the preformed dimethoxyfluoroborane mixture. The reaction was stirred at −78° C. for 30 minutes, warmed to room temperature for 30 minutes, and then quenched with water (10 ml). The reaction mixture was extracted with diethyl ether (4×50 ml). The combined organic extracts were dried over MgSO4 and concentrated in vacuo. To purify, the residue was dissolved in diethyl ether (10 ml) and washed with an aqueous solution of 10% NaOH (50 ml). The aqueous layer was acidified and extracted with ethyl acetate (3×40 ml). The combined ethyl acetate extracts were dried over MgSO4 and concentrated in vacuo to afford a mixture of the title compound and its corresponding regioisomer as a white solid (0.862 g). The reaction was stirred at −78° C. for 30 minutes quenched with water (10 ml) The reaction mixture was extracted with diethyl ether (4×50 ml) The combined organic extracts were dried over MgSO4 concentrated in vacuo To purify the residue was dissolved in diethyl ether (10 ml) washed with an aqueous solution of 10% NaOH (50 ml) extracted with ethyl acetate (3×40 ml) The combined ethyl acetate extracts were dried over MgSO4 concentrated in vacuo to afford

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

Procedure: Chlorine and p-nitrotrifluoromethoxybenzene (10.7 parts) were fed simultaneously at a molar ratio of 3:1, Cl2 : organic reactant, into a vapor phase reactor maintained at 300° to 320° C. over a 30 minute period to yield 8.2 parts of p-chlorotrifluoromethoxybenzene (83% yield). The structure of the product was confirmed by gas chromatographic-mass spectrum and F19 nuclear magnetic resonance analysis. organic reactant, into a vapor phase reactor maintained at 300° to 320° C. over a 30 minute period