1-chloro-3-(trifluoromethyl)benzene

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

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

Procedure: In an analogous manner to that described in the preceding paragraph, hydroquinone and 3-trifluoromethyl-chlorobenzene in the presence of a catalytic amount of copper powder yield p-(α,α,α-trifluoro-m-tolyloxy)-phenol which distils in the bulb-tube at 140° C./0.05 Torr; nD20 =1.5370.

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

Procedure: 33 g of zinc powder, 33 g of triphenylphosphine, 5 of sodium iodide, 2.2 g of nickel(II) chloride and 200 ml of dimethylformamide were mixed under a nitrogen atmosphere and the mixture was initially introduced into the reaction vessel. The mixture was kept at 50° to 60° C. for half an hour, after which a suspension coloured deep red-brown was present. A solution containing 20.2 g (0.11 mol) of 3-chloro-benzotrifluoride, 38.2 g (0.22 mol) of methyl 4-chloro-benzoate and 100 ml of dimethylformamide was added dropwise to this suspension in the course of half an hour. After 6 hours at 80° C., the reaction mixture was introduced into 500 ml of chloroform and filtered. The residue on the filter was boiled up in 400 ml of toluene and filtered off hot. After cooling, 15 g of dimethyl biphenyl-4,4'-dicarboxylate (50.5% of theory--based on the methyl 4-chloro-benzoate employed) of melting point 213° to 214° C. were obtained. The filtrate was extracted by shaking with dilute aqueous hydrochloric acid and with water and the organic phase was dried over sodium sulphate and concentrated. The resulting residue was distilled. 6.4 g of 3,3'-bis-(trifluoromethyl)-biphenyl (20% of theory--based on the 3-chloro-benzotrifluoride employed) and a total of 16 g of methyl 4-(3-trifluoromethylphenyl)-benzoate (52% of theory--based on the 3-chloro-benzotrifluoride employed) of boiling point 125° C. to 130° C. under 0.1 to 0.3 mbar were obtained in this manner. the mixture was initially introduced into the reaction vessel The mixture was kept at 50° to 60° C. for half an hour was added dropwise to this suspension in the course of half an hour filtered filtered off hot After cooling were obtained The filtrate was extracted the organic phase was dried over sodium sulphate concentrated The resulting residue was distilled were obtained in this manner

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

Procedure: To a solution of 1-chloro-3-(trifluoromethyl)benzene (1.0 g, 5.5 mmol) in THF (10.0 mL) was added 2.5 M of n-BuLi in hexane (2.2 mL) at −78° C. and stirred for 1 h. Propylene oxide (370 mg, 6.4 mmol) was added to the reaction mixture at −78° C. and slowly warmed to rt. The reaction mixture was stirred for an additional 30 min. The reaction mixture was quenched with sat. aq. NH4Cl and extracted with EtOAc. The organic layer was washed with brine, dried over anhydrous Na2SO4, and the solvent was removed under reduced pressure to give a yellow oil. The material was purified by silica gel chromatography using Hexane/EtOAc (80:20) as eluent to yield the desired product as a yellow oil. 1H NMR (CDCl3, 400 MHz): δ=1.33 (d, J=6.1 Hz, 3H), 1.40 (d, J=6.3 Hz, 1H), 3.08-3.22 (m, 2H), 4.21-4.33 (m, 1H), 7.29-7.34 (m, 1H), 7.58-7.64 (m, 2H). The reaction mixture was stirred for an additional 30 min The reaction mixture was quenched with sat. aq. NH4Cl extracted with EtOAc The organic layer was washed with brine dried over anhydrous Na2SO4 the solvent was removed under reduced pressure to give a yellow oil The material was purified by silica gel chromatography

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

Procedure: In an analogous manner to that described in the preceding paragraph, hydroquinone and 3-trifluoromethyl-chlorobenzene in the presence of a catalytic amount of copper powder yield p-(α,α,α-trifluoro-m-tolyloxy)-phenol which distils in the bulb-tube at 140° C./0.05 Torr; nD20 =1.5370.

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

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

Procedure: 0.745 g (7.2 mmol) of styrene, 38.7 mg (120 μmol) of NBu4Br, 6.7 mg (30 μmol) of palladium acetate and 26.7 mg (120 μmol) of phenyldi(t-butyl)phosphine are weighed into a Schlenk vessel. 1.08 g (6 mmol) of 3-chlorobenzotrifluoride and 1.53 ml (7.2 mmol) of dicyclohexylmethylamine and also 3.5 ml of dimethylacetamide are then added. The Schlenk vessel is placed in a heating bath at 130° C. and the contents are stirred. After 4 hours, the contents are poured into 30 ml of water and the product is extracted by shaking with t-butyl methyl ether. After drying the organic phase over MgSO4, the solvent is removed under reduced pressure and the product is isolated. Yellowish, crystalline solid, yield: 1.43 g (96% of theory). The Schlenk vessel is placed in a heating bath at 130° C. the product is extracted by shaking with t-butyl methyl ether After drying the organic phase over MgSO4 the solvent is removed under reduced pressure the product is isolated

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

Procedure: 0.29 g (12.1 mmole) of magnesium turnings was stirred in 5 ml of ether of analysis purity. 2.35 g (12.1 mmole) of 3-chlorobenzotrifluoride dissolved in 5 ml of ether were added dropwise so that the reaction mixture boiled gently. After completion of the addition the reaction mixture was stirred for a further hour at RT. 2.51 g (10.1 mmole) of the 2-[dimethylamino-(4-fluorophenyl)methyl]cyclohexanone prepared according to Example 41 were dissolved in 5 ml of ether, added dropwise to the Grignard reagent while cooling in an ice bath, and stirred for 15 hours at RT. The reaction mixture was worked up by adding 15 ml of saturated ammonium chloride solution while cooling in an ice bath, and was extracted three times at RT with 15 ml of ether each time. The combined organic extracts were dried over sodium sulfate, filtered, and concentrated by evaporation on a rotary evaporator (500 to 10 mbar). 4.15 g of crude base (101% of theory) were obtained, from which 3.10 g of 2-[dimethylamino-(4-fluorophenyl)methyl]-1-(3-trifluoromethylbenzyl)cyclo-hexanol, hydrochloride (69.1% of theory) were obtained according to the procedure described in Example 1 (3rd Stage) with chlorotrimethylsilane/water in 2-butanone. The hydrochloride decomposes on heating above 210° C. were added dropwise so that the reaction mixture After completion of the addition the reaction mixture while cooling in an ice bath stirred for 15 hours at RT while cooling in an ice bath was extracted three times at RT with 15 ml of ether each time The combined organic extracts were dried over sodium sulfate filtered concentrated by evaporation on a rotary evaporator (500 to 10 mbar)

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

Procedure: From 3-chlorobenzotrifluoride (180 mg, 1 mmol), AlCl3 (400 mg, 3 mmol) and fluorobenzene (96 mg, 1 mmol), light yellow oil (384 mg, 132% crude).

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

Procedure: From 3-chlorobenzotrifluoride (180 mg, 1 mmol), AlCl3 (400 mg, 3 mmol) and fluorobenzene (96 mg, 1 mmol), light yellow oil (384 mg, 132% crude).

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

Procedure: from hydroquinone and 3-chlorobenzotrifluoride with the addition of a catalytic amount of copper powder there is obtained p-(α,α,α-trifluoro-m-tolyloxy)-phenol which distils in a bulb-tube at 140° C./0.05 Torr; nD20 =1.5370.

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

Procedure: In an analogous manner to that described in the preceding paragraph, hydroquinone and 3-trifluoromethyl-chlorobenzene in the presence of a catalytic amount of copper powder yield p-(α,α,α-trifluoro-m-tolyloxy)-phenol which distils in the bulb-tube at 140° C./0.05 Torr; nD20 =1.5370.