1-(4-fluoro-2-phenylmethoxyphenyl)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:; See reaction.notes.procedure_details.

Procedure: A mixture of 11 parts of 1-[4-fluoro-2-(phenylmethoxy)phenyl]ethanone, 8.48 parts of 3-chlorobenzenecarboperoxoic acid and 260 parts of dichloromethane was stirred for 5 days at room temperature. The precipitate was filtered off and the filtrate was stirred in a saturate thiosulfurate solution for 15 minutes. The organic layer was separated and stirred in a saturate hydrogen carbonate solution for 15 minutes. The organic layer was separated, washed with water, dried, filtered and evaporated. The solid residue was stirred in 240 parts of methanol. 5.3 Parts of sodium methoxide were added portionwise. After complete addition, the whole was stirred for 1 hour at room temperature. After evaporation in vacuo at 50° C., the residue was stirred in water and acidified with a hydrochloric acid solution 3N. Trichloromethane was added, the organic layer was separated, washed twice with water, dried, filtered and evaporated, yielding 10 parts (93%) of 4-fluoro-2-(phenylmethoxy)phenol as a residue (intermediate 77). The precipitate was filtered off the filtrate was stirred in a saturate thiosulfurate solution for 15 minutes The organic layer was separated stirred in a saturate hydrogen carbonate solution for 15 minutes The organic layer was separated washed with water dried filtered evaporated The solid residue was stirred in 240 parts of methanol 5.3 Parts of sodium methoxide were added portionwise After complete addition the whole was stirred for 1 hour at room temperature After evaporation in vacuo at 50° C. the residue was stirred in water Trichloromethane was added the organic layer was separated washed twice with water dried filtered evaporated

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

Procedure: A mixture of 11 parts of 1-[4-fluoro-2-(phenylmethoxy)phenyl]ethanone, 8.48 parts of 3-chlorobenzenecarboperoxoic acid and 260 parts of dichloromethane was stirred for 5 days at room temperature. The precipitate was filtered off and the filtrate was stirred in a saturate thiosulfurate solution for 15 minutes. The organic layer was separated and stirred in a saturate hydrogen carbonate solution for 15 minutes. The organic layer was separated, washed with water, dried, filtered and evaporated. The solid residue was stirred in 240 parts of methanol. 5.3 Parts of sodium methoxide were added portionwise. After complete addition, the whole was stirred for 1 hour at room temperature. After evaporation in vacuo at 50° C., the residue was stirred in water and acidified with a hydrochloric acid solution 3N. Trichloromethane was added, the organic layer was separated, washed twice with water, dried, filtered and evaporated, yielding 10 parts (93%) of 4-fluoro-2-(phenylmethoxy)phenol as a residue (intermediate 77). The precipitate was filtered off the filtrate was stirred in a saturate thiosulfurate solution for 15 minutes The organic layer was separated stirred in a saturate hydrogen carbonate solution for 15 minutes The organic layer was separated washed with water dried filtered evaporated The solid residue was stirred in 240 parts of methanol 5.3 Parts of sodium methoxide were added portionwise After complete addition the whole was stirred for 1 hour at room temperature After evaporation in vacuo at 50° C. the residue was stirred in water Trichloromethane was added the organic layer was separated washed twice with water dried filtered evaporated

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

Procedure: A mixture of 13 parts of 1-(4-fluoro-2-hydroxyphenyl)ethanone, 14.9 parts of (chloromethyl)benzene, 16.4 parts of potassium carbonate, 0.1 parts of potassium iodide and 120 parts of 2-propanone was stirred overnight at reflux temperature. The reaction mixture was evaporated. The reaction mixture was poured into water. The product was extracted three times with trichloromethane. The combined extracts were dried, filtered and evaporated. The residue was crystallized from a mixture of 2-propanol and water. The product was filtered off and dried, yielding 11 parts (58%) of 1-[4-fluoro-2-(phenylmethoxy)phenyl]ethanone (intermediate 76). at reflux temperature The reaction mixture was evaporated The reaction mixture was poured into water The product was extracted three times with trichloromethane The combined extracts were dried filtered evaporated The residue was crystallized from a mixture of 2-propanol and water The product was filtered off dried

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

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

Procedure: A mixture of 13 parts of 1-(4-fluoro-2-hydroxyphenyl)ethanone, 14.9 parts of (chloromethyl)benzene, 16.4 parts of potassium carbonate, 0.1 parts of potassium iodide and 120 parts of 2-propanone was stirred overnight at reflux temperature. The reaction mixture was evaporated. The reaction mixture was poured into water. The product was extracted three times with trichloromethane. The combined extracts were dried, filtered and evaporated. The residue was crystallized from a mixture of 2-propanol and water. The product was filtered off and dried, yielding 11 parts (58%) of 1-[4-fluoro-2-(phenylmethoxy)phenyl]ethanone (intermediate 76). at reflux temperature The reaction mixture was evaporated The reaction mixture was poured into water The product was extracted three times with trichloromethane The combined extracts were dried filtered evaporated The residue was crystallized from a mixture of 2-propanol and water The product was filtered off dried

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

Procedure: A mixture of 11 parts of 1-[4-fluoro-2-(phenylmethoxy)phenyl]ethanone, 8.48 parts of 3-chlorobenzenecarboperoxoic acid and 260 parts of dichloromethane was stirred for 5 days at room temperature. The precipitate was filtered off and the filtrate was stirred in a saturate thiosulfate solution for 15 minutes. The organic layer was separated and stirred in a saturate hydrogen carbonate solution for 15 minutes. The organic layer was separated, washed with water, dried, filtered and evaporated. The solid residue was stirred in 240 parts of methanol. 5.3 Parts of sodium methoxide were added portionwise. After complete addition, the whole was stirred for 1 hour at room temperature. After evaporation in vacuo at 50° C., the residue was stirred in water and acidified with a hydrochloric acid solution 3N. Trichloromethane was added, the organic layer was separated, washed twice with water, dried, filtered and evaporated, yielding 10 parts (93%) of 4-fluoro-2-(phenylmethoxy)phenol as a residue (intermediate 77). The precipitate was filtered off the filtrate was stirred in a saturate thiosulfate solution for 15 minutes The organic layer was separated stirred in a saturate hydrogen carbonate solution for 15 minutes The organic layer was separated washed with water dried filtered evaporated The solid residue was stirred in 240 parts of methanol 5.3 Parts of sodium methoxide were added portionwise After complete addition the whole was stirred for 1 hour at room temperature After evaporation in vacuo at 50° C. the residue was stirred in water Trichloromethane was added the organic layer was separated washed twice with water dried filtered evaporated

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

Procedure: A mixture of 3 parts of 1-(4-fluoro-2-hydroxyphenyl)ethanone, 14.9 parts of (chloromethyl)benzene, 16.4 parts of potassium carbonate, 0.1 parts of potassium iodide and 120 parts of 2-propanone was stirred overnight at reflux temperature. The reaction mixture was evaporated. The reaction mixture was poured into water. The product was extracted three times with trichloromethane. The combined extracts were dried, filtered and evaporated. The residue was crystallized from a mixture of 2-propanol and water. The product was filtered off and dried, yielding 11 parts (58%) of 1-[4-fluoro-2-(phenylmethoxy)phenyl]ethanone (intermediate 76). at reflux temperature The reaction mixture was evaporated The reaction mixture was poured into water The product was extracted three times with trichloromethane The combined extracts were dried filtered evaporated The residue was crystallized from a mixture of 2-propanol and water The product was filtered off dried

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

Procedure: Phenyltrimethylammonium tribromide (1.55 g, 4.13 mmol) was added to a solution of 2′-(benzyloxy)-4′-fluoroacetophenone (1.01 g, 4.13 mmol) in THF (10 mL), and the mixture stirred at room temperature for 45 minutes, over which time the orange solution faded and a white precipitate formed. Tlc analysis (9:1 hexane:EtOAc) showed the reaction to be complete. The mixture was poured into water (20 mL) and extracted with ether (2×50 mL). The combined ethereal extracts were dried (MgSO4) and the solvents removed in vacuo to give crude 2′-(benzyloxy)-2-bromo-4′-fluoroacetophenone as a colourless oil, which was used in the following step without purification. Rf 0.47 (9:1 hexane:EtOAc); δH (CDCl3) 7.89 (1H, dd, J=9.4 and 6.9 Hz), 7.45-7.40 (5H, m), 6.77-6.74 (2H, m), 5.15 (2H, s), 4.47 (2H, s); LCMS retention time 2.75 min, M+H+ 323.3/325.3. a white precipitate formed the reaction extracted with ether (2×50 mL) The combined ethereal extracts were dried (MgSO4) the solvents removed in vacuo

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

Procedure: Potassium carbonate (4.02 g, 29.10 mmol) was added to a solution of 4′-fluoro-2′-hydroxyacetophenone (2.0 mL, 2.56 g, 16.60 mmol) in DMF (15 mL). Benzyl bromide (2.07 mL, 2.98 g, 17.50 mmol) was added dropwise over 5 minutes at room temperature, and the mixture stirred for 18 h. The mixture was poured into hydrochloric acid (1.0 M in H2O; 200 mL) and extracted with ethyl acetate (2×100 mL). The combined organic extracts were dried (MgSO4) and the solvents removed in vacuo. Pure 2′-(benzyloxy)-4′-fluoroacetophenone (3.94 g, 97%) was obtained as a white powder after trituration with hexane. Rf 0.44 (9:1 hexane:EtOAc); δH (CDCl3) 7.82 (1H, dd, J=8.6 and 7.0 Hz), 7.43-7.38 (5H, m), 6.75-6.69 (2H, m), 5.13 (2H, s), 2.56 (3H, d, J=3.2 Hz); LCMS retention time 2.68 min, M+H+ 245.1. extracted with ethyl acetate (2×100 mL) The combined organic extracts were dried (MgSO4) the solvents removed in vacuo

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

Procedure: A mixture of 11 parts of 1-[4-fluoro-2-(phenylmethoxy)phenyl]ethanone, 8.48 parts of 3-chlorobenzenecarboperoxoic acid and 260 parts of dichloromethane was stirred for 5 days at room temperature. The precipitate was filtered off and the filtrate was stirred in a saturate thiosulfurate solution for 15 minutes. The organic layer was separated and stirred in a saturate hydrogen carbonate solution for 15 minutes. The organic layer was separated, washed with water, dried, filtered and evaporated. The solid residue was stirred in 240 parts of methanol. 5.3 Parts of sodium methoxide were added portionwise. After complete addition, the whole was stirred for 1 hour at room temperature. After evaporation in vacuo at 50° C., the residue was stirred in water and acidified with a hydrochloric acid solution 3N. Trichloromethane was added, the organic layer was separated, washed twice with water, dried, filtered and evaporated, yielding 10 parts (93%) of 4-fluoro-2-(phenylmethoxy)phenol as a residue (intermediate 77). The precipitate was filtered off the filtrate was stirred in a saturate thiosulfurate solution for 15 minutes The organic layer was separated stirred in a saturate hydrogen carbonate solution for 15 minutes The organic layer was separated washed with water dried filtered evaporated The solid residue was stirred in 240 parts of methanol 5.3 Parts of sodium methoxide were added portionwise After complete addition the whole was stirred for 1 hour at room temperature After evaporation in vacuo at 50° C. the residue was stirred in water Trichloromethane was added the organic layer was separated washed twice with water dried filtered evaporated