1-(4-fluorophenyl)propan-1-one

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:; See reaction.notes.procedure_details.

Procedure: A solution of butyllithium, 1.6M in hexanes (230 ml,0.368 mol, Aldrich) was added dropwise over 0.5 hr, with rapid mechanical stirring, to a solution of triethyl phosphonoacetate (78.9 g, 0.351 mol, Aldrich) in tetrahydrofuran (800 ml, anhydrous, Aldrich) at <5° C. while blanketed with a nitrogen atmosphere. This solution was stirred for an additional 0.25 hr and cooled to -5° C. with a methanol:ice bath and a solution of 4'-fluoropropiophenone (50 g,0.328 mol, Aldrich) in tetrahydrofiran (50 ml) was then added in one portion. Stirring was continued for 18 hr without additional cooling. The solution was concentrated to a golden yellow sludge by spin evaporation in vacuo and diluted to 1000 ml with ethyl acetate. After washing with deionized water (3×100 ml) this solution was concentrated by spin evaporation in vacuo. Distillation at reduced pressure gave 45.65 g (63%) of ethyl 3-(4-fluorophenyl)pentenoate as a mixture of (E) and (Z) isomers (ratio 1:1) contaminated with 30% of triethyl phosphonoacetate as a clear liquid, b.p. 140°-146° C. at aspirator pressure; Stirring was continued for 18 hr without additional cooling The solution was concentrated to a golden yellow sludge by spin evaporation in vacuo diluted to 1000 ml with ethyl acetate After washing with deionized water (3×100 ml) this solution was concentrated by spin evaporation in vacuo Distillation at reduced pressure

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

Procedure: A mixture of 15.2 g. (0.10 mole) of 4'-fluoropropiophenone, 8.2 g. (0.10 mole) of dimethylamine hydrochloride, 3.6 g. (0.12 mole) of paraformaldehyde in 20 ml. of absolute alcohol was stirred at 95°-100°C for three hours. The mixture is cooled and the precipitated product is filtered. The product is dissolved in water, made alkaline with sodium hydroxide. The free base is extracted into ether. The ether layer is dried over anhydrous sodium sulfate and concentrated in vacuo to give 3-dimethylamino-4'-fluoro-2methylpropiophenone A mixture of 15.2 g The mixture is cooled the precipitated product is filtered The product is dissolved in water The free base is extracted into ether The ether layer is dried over anhydrous sodium sulfate concentrated in vacuo

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

Procedure: A mixture of 15.2 g. (0.10 mole) of 4'-fluoropropiophenone, 8.2 g. (0.10 mole) of dimethylamine hydrochloride, 3.6 g. (0.12 mole) of paraformaldehyde in 20 ml. of absolute alcohol was stirred at 95°-100°C for three hours. The mixture is cooled and the precipitated product is filtered. The product is dissolved in water, made alkaline with sodium hydroxide. The free base is extracted into ether. The ether layer is dried over anhydrous sodium sulfate and concentrated in vacuo to give 3-dimethylamino-4'-fluoro-2methylpropiophenone A mixture of 15.2 g The mixture is cooled the precipitated product is filtered The product is dissolved in water The free base is extracted into ether The ether layer is dried over anhydrous sodium sulfate concentrated in vacuo

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

Procedure: A mixture of 45.7 g. (0.3 moles) of 4'-fluoropropiophenone, 9 g. (0.3 moles) of paraformaldehyde, 4 g. (0.03 mole) of anhydrous potassium carbonate and 200 ml. of methyl alcohol is stirred at 35°C for two days. The reaction is quenched in water and acidified with hydrochloric acid. The product is extracted into benzene. The benzene layer is washed with water and concentrated in vacuo to give 4'-fluoro-3-hydroxy-2-methylpropiophenone. A mixture of 45.7 g The reaction is quenched in water The product is extracted into benzene The benzene layer is washed with water concentrated in vacuo

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

Procedure: A mixture of 45.7 g. (0.3 moles) of 4'-fluoropropiophenone, 9 g. (0.3 moles) of paraformaldehyde, 4 g. (0.03 mole) of anhydrous potassium carbonate and 200 ml. of methyl alcohol is stirred at 35°C for two days. The reaction is quenched in water and acidified with hydrochloric acid. The product is extracted into benzene. The benzene layer is washed with water and concentrated in vacuo to give 4'-fluoro-3-hydroxy-2-methylpropiophenone. A mixture of 45.7 g The reaction is quenched in water The product is extracted into benzene The benzene layer is washed with water concentrated in vacuo

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

Procedure: 3 g (0.019 mole) of 4-(4-piperidyl)-1H-imidazole and 2.88 g (0.019 mole) of para-fluoropropiophenone are stirred in 70 cm3 of dimethylformamide for 5 minutes. 4 g (0.037 mole) of disodium carbonate and 0.2 g (0.0012 mole) of potassium iodide are added and the solution is brought to 160° C. for 3 hours. After being cooled, the solution is poured into 200 cm3 of water and stirred for 1 hour. The precipitate formed is drained, washed with water, dried and recrystallized in acetonitrile. After being cooled The precipitate formed washed with water dried recrystallized in acetonitrile

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

Procedure: 3 g (0.019 mole) of 4-(4-piperidyl)-1H-imidazole and 2.88 g (0.019 mole) of para-fluoropropiophenone are stirred in 70 cm3 of dimethylformamide for 5 minutes. 4 g (0.037 mole) of disodium carbonate and 0.2 g (0.0012 mole) of potassium iodide are added and the solution is brought to 160° C. for 3 hours. After being cooled, the solution is poured into 200 cm3 of water and stirred for 1 hour. The precipitate formed is drained, washed with water, dried and recrystallized in acetonitrile. After being cooled The precipitate formed washed with water dried recrystallized in acetonitrile

Conditions: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The title compound was prepared by following general procedure 3. DMSO was added to NaH (1 equiv.) and heated to 65° C. for 1 h. THF was added at the same temperature and heated for another 10 min. After 10 min., the reaction mixture was cooled to 0° C. Trimethylsulfonium iodide (1 equiv.) was added and stirred for 10 min. after which the solution of 1-(4-fluorophenyl) propan-1-one (1 equiv.) in THF was added dropwise. After complete addition, the reaction mixture was stirred at RT for 2 h. The product was detected by LCMS and the reaction mixture was poured into ice water, extracted in diethyl ether (4×50 mL), dried over Na2SO4 and concentrated at 25° C. to obtain the product. heated for another 10 min the reaction mixture was cooled to 0° C was added dropwise After complete addition extracted in diethyl ether (4×50 mL) dried over Na2SO4 concentrated at 25° C. to obtain the product

Conditions: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The title compound was prepared by following general procedure 3. DMSO was added to NaH (1 equiv.) and heated to 65° C. for 1 h. THF was added at the same temperature and heated for another 10 min. After 10 min., the reaction mixture was cooled to 0° C. Trimethylsulfonium iodide (1 equiv.) was added and stirred for 10 min. after which the solution of 1-(4-fluorophenyl) propan-1-one (1 equiv.) in THF was added dropwise. After complete addition, the reaction mixture was stirred at RT for 2 h. The product was detected by LCMS and the reaction mixture was poured into ice water, extracted in diethyl ether (4×50 mL), dried over Na2SO4 and concentrated at 25° C. to obtain the product. heated for another 10 min the reaction mixture was cooled to 0° C was added dropwise After complete addition extracted in diethyl ether (4×50 mL) dried over Na2SO4 concentrated at 25° C. to obtain the product