2-chloro-1-(4-fluorophenyl)ethanone

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

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

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

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

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

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

Conditions: temp:23.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 0.12 mol of ethynylmagnesium bromide in 300 mL of dry THF at 23° C. was added 15.5 g (90 mmol) of 2-chloro-4'-fluoro-acetophenone as a solid. The mixture stirred at 23° C. for 24 hours when it was quenched with 15 mL of saturated NH4Cl and poured int 250 mL of diethyl ether. The ether layer was separated and washed with H2O, dried (MgSO4) and concentrated. The residue was added to 300 mL of dry diethyl ether and 3.6 g (90 mmol) of pulverized NaOH was added. The reaction mixture was stirred at 23° C. for 3 hours, then the ether was washed twice with 100 mL of H2O and once with saturated brine. The organic layer was dried (MgSO4), concentrated and distillation (b.p. 55°-58° C. at 0.34 mmHg) provided 9.5 g (66%) of 3,4-epoxy- 3-(4'-fluorophenyl)-1-butyne as a liquid, homogeneous by spectroscopic criteria; IR (film) 3275, 1595, 1505, 1218 cm-1 ; 1HNMR (80 MHz, CDCl3) δ 7.45 (m, 2H), 7.15 (m, 2H), 3.20 (ABq, 2H, J=8.0 Hz, ΔνAB =39.2 Hz), 2.51 (s, 1H). was quenched with 15 mL of saturated NH4Cl poured int 250 mL of diethyl ether The ether layer was separated washed with H2O dried (MgSO4) concentrated was added The reaction mixture was stirred at 23° C. for 3 hours the ether was washed twice with 100 mL of H2O and once with saturated brine The organic layer was dried (MgSO4) concentrated distillation (b.p. 55°-58° C. at 0.34 mmHg)

Conditions: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 23.1 g (0.16 mol) of propargylmagnesium bromide (J. Am. Chem. Soc., 83, 1686, 1961) in 50 mL of dry diethyl ether at 25° C. was added 20.0 g (0.115 mol) of 2-chloro-4'-fluoroacetophenone in 150 mL of diethyl ether over a 0.25 hour period. The solution was stirred at 25° C. for 15 hours and then quenched with 50 mL of saturated NH4Cl. The layers were separated and the aqueous phase extracted twice with 100 mL diethyl ether. The combined ether extracts were dried (MgSO4) and the solvent removed at reduced pressure. This residue was dissolved in 250 mL of dry diethyl ether and added to 4.9 g of pulverized NaOH. This mixture was stirred at 24° C. for 3.5 hours and then 0.5 g of NaOH was added. After an additional 2.5 hours, the mixture was poured into 100 mL of H2O and extracted with diethyl ether. The ether layer was separated, dried (MgSO4) and concentrated under reduced pressure. Distillation under reduced pressure (94°-95° C. at 0.65 mmHg) yielded 16 g (79%) of 4,5-epoxy-4-(4'-fluorophenyl)-1-pentyne as an oil, homogeneous by TLC and spectroscopic criteria; Rf 0.75 (1:1 hexanes-diethyl ether): IR (film) 3290, 1600, 1505, 1225 cm-1 ; 1HNMR (300 MHz, CDCl3) δ 7.5-7.4 (m, 2H), 7.1-7.05 (m, 2H, 3.02 (ABq, 2H, JAB =6.0 Hz, ΔνAB =119.8 Hz), 2.92 (t, 2H, J=2 Hz), 2.07 (t, 1H, J=2 Hz). quenched with 50 mL of saturated NH4Cl The layers were separated the aqueous phase extracted twice with 100 mL diethyl ether The combined ether extracts were dried (MgSO4) the solvent removed at reduced pressure This residue was dissolved in 250 mL of dry diethyl ether added to 4.9 g of pulverized NaOH This mixture was stirred at 24° C. for 3.5 hours 0.5 g of NaOH was added After an additional 2.5 hours the mixture was poured into 100 mL of H2O extracted with diethyl ether The ether layer was separated dried (MgSO4) concentrated under reduced pressure Distillation under reduced pressure (94°-95° C. at 0.65 mmHg)

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

Procedure: 2-Chloro-1-(4-fluorophenyl)ethanone (10 g, 57.4 mmol) is dissolved in acetonitrile (400 mL). The solution is cooled to 0° C. and diallylamine (15.6 mL, 126.2 mmol) is added. After 1 hour, the mixture is poured into water (500 mL) and extracted twice with ethyl acetate (400 mL). The organic extracts are combined, washed with brine (1×200 mL), dried over sodium sulfate, filtered, and concentrated to give the crude title compound (15.84 g, 118%). ES/MS (m/e): 234 (M+H). extracted twice with ethyl acetate (400 mL) washed with brine (1×200 mL) dried over sodium sulfate filtered concentrated

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

Procedure: To a 1 L volume four-necked flask, sodium methanesulfinate (31.3 g), 4-fluorophenacyl chloride (21-b) (4.8.1 g), and ethanol (300 ml) were added under a nitrogen atmosphere, and heated to reflux for 1 hour. After the mixture was cooled to room temperature, water (500 ml) was added. The precipitated solids were collected by filtration, washed with water, and dried. The solids were dissolved in ethyl acetate, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resulting residue was purified by recrystallization (hexane-ethyl acetate) to give 51.9 g of 1-(4-fluorophenyl)-2-methylsulfonylethan-1-one (7-2-3). heated to reflux for 1 hour The precipitated solids were collected by filtration washed with water dried The solids were dissolved in ethyl acetate dried over anhydrous sodium sulfate concentrated under reduced pressure The resulting residue was purified by recrystallization (hexane-ethyl acetate)

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

Procedure: In a manner similar to that previously described, 4.2 parts of 1-[2,4-dichloro-β-(2,4-dichlorobenzyloxy)phenethyl]imidazole, 1.7 parts of 2-chloro-4'-fluoroacetophenone and 40 parts of methylene chloride are mixed together and stirred at reflux temperature for 15 hours. Thereafter, the solvent is evaporated under reduced pressure and the residue triturated in 4-methyl-2-pentanone. The solid is recovered by filtration and crystallized from acetonitrile to obtain a purified 1-[2,4-dichloroβ-(2,4-dichlorobenzyloxy)phenethyl]-3-(p-fluorobenzoylmethyl)imidazolium chloride product, m.p. 181° C. at reflux temperature for 15 hours Thereafter, the solvent is evaporated under reduced pressure the residue triturated in 4-methyl-2-pentanone The solid is recovered by filtration crystallized from acetonitrile

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