Ethanol, 2-[(2,6-dichlorophenyl)Methoxy]-

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 22.1 g of 2-(2,6-dichlorobenzyloxy)ethanol and 10.1 g of triethylamine were dissolved in 200 ml of toluene, then cooled to 0° C. To this solution was dropwise added a solution of 34.5 g of 2-[4-(4-trifluoromethylphenoxy)phenoxy]propionyl chloride in 50 ml of toluene at 0° to 10° C. After the dropwise addition, the reaction mixture was gradually heated and, at 40° C., it was stirred for one hour to complete the reaction. After cooling the reaction solution to room temperature, it was washed successively with 1% strength by weight sodium hydroxide aqueous solution and water, then dehydrated. After distilling off toluene under reduced pressure, the resulting colorless, viscous, oily product was allowed to stand for about 1 month to obtain 49.2 g of crystalline 2-(2,6-dichlorobenzyloxy)ethyl 2-[4-(4-trifluoromethylphenoxy)phenoxy]propionate. m.p. 51° to 53° C. After the dropwise addition the reaction mixture was gradually heated and, at 40° C. the reaction After cooling the reaction solution to room temperature it was washed successively with 1% strength by weight sodium hydroxide aqueous solution and water After distilling off toluene under reduced pressure to stand for about 1 month

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 50% aq NaOH (1.89 L), 2-(2,6-dichlorobenzyloxy)ethanol (473.2 g), 1,6-dibromohexane (2.44 kg, 5 eq) and tetrabutylammonium bromide (34.1 g, 5 mol %) in toluene (1.89 L) was heated to 55-60° C. for 8-20 h. On cooling water (558 mL) and toluene (558 mL) were added. The aqueous phase was separated and diluted with water (1 L) then back extracted with toluene (1.1 L). The combined toluene extracts were washed twice with water (2.2 L), then evaporated to dryness on a rotary evaporator. The excess 1,6-dibromohexane was removed using a wiped film evaporator, and the resulting crude product chromatographed on silica (5 kg Biotage), eluting with 5% ethyl acetate in petrol 60/80, to give the title compound (503.2 g)—LC RT=7.0 min. were added The aqueous phase was separated diluted with water (1 L) then back extracted with toluene (1.1 L) The combined toluene extracts were washed twice with water (2.2 L) evaporated to dryness on a rotary evaporator The excess 1,6-dibromohexane was removed a wiped film evaporator the resulting crude product chromatographed on silica (5 kg Biotage) eluting with 5% ethyl acetate in petrol 60/80

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 50% aq NaOH (1.89 L), 2-(2,6-dichlorobenzyloxy)ethanol (473.2 g), 1,6-dibromohexane (2.44 kg, 5 eq) and tetrabutylammonium bromide (34.1 g, 5 mol %) in toluene (1.89 L) was heated to 55-60° C. for 8-20 h. On cooling water (558 mL) and toluene (558 mL) were added. The aqueous phase was separated and diluted with water (1 L) then back extracted with toluene (1.1 L). The combined toluene extracts were washed twice with water (2.2 L), then evaporated to dryness on a rotary evaporator. The excess 1,6-dibromohexane was removed using a wiped film evaporator, and the resulting crude product chromatographed on silica (5 kg Biotage), eluting with 5% ethyl acetate in petrol 60/80, to give the title compound (503.2 g)—LC RT=7.0 min. were added The aqueous phase was separated diluted with water (1 L) then back extracted with toluene (1.1 L) The combined toluene extracts were washed twice with water (2.2 L) evaporated to dryness on a rotary evaporator The excess 1,6-dibromohexane was removed a wiped film evaporator the resulting crude product chromatographed on silica (5 kg Biotage) eluting with 5% ethyl acetate in petrol 60/80

反応条件: temp:57.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Sodium methoxide (104.4 g, 1.93 mol) was added portionwise to ethylene glycol (3.74 L) under N2, keeping the temperature below 35° C. After 1-2 h, 2,6-dichlorobenzylbromide (400 g, 1.67 mol) was added and the mixture heated to 55-60° C. for 1 h. On cooling to 20° C. water (2.14 L) was added and the mixture extracted with ethyl acetate (2.14 L). The aqueous layer was separated and extracted twice with ethyl acetate (2.14 L, 1.28 L). The combined organic extracts were washed with water (2.14 L) then evaporated to dryness to afford a colourless oil (371.8 g)—LC RT=4 min. This may be chromatographed on silica (Biotage) eluting with 10% ethyl acetate in 60/80 petrol to afford the title compound. the temperature below 35° C was added the mixture extracted with ethyl acetate (2.14 L) The aqueous layer was separated extracted twice with ethyl acetate (2.14 L, 1.28 L) The combined organic extracts were washed with water (2.14 L) then evaporated to dryness

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 50% aq NaOH (1.89 L), 2-(2,6-dichlorobenzyloxy)ethanol (473.2 g), 1,6-dibromohexane (2.44 kg, 5 eq) and tetrabutylammonium bromide (34.1 g, 5 mol %) in toluene (1.89 L) was heated to 55–60° C. for 8–20 h. On cooling water (558 mL) and toluene (558 mL) were added. The aqueous phase was separated and diluted with water (1 L) then back extracted with toluene (1.1 L). The combined toluene extracts were washed twice with water (2.2 L), then evaporated to dryness on a rotary evaporator. The excess 1,6-dibromohexane was removed using a wiped film evaporator, and the resulting crude product chromatographed on silica (5 kg Biotage), eluting with 5% ethyl acetate in petrol 60/80, to give the title compound (503.2 g)—LC RT=7.0 min. were added The aqueous phase was separated diluted with water (1 L) then back extracted with toluene (1.1 L) The combined toluene extracts were washed twice with water (2.2 L) evaporated to dryness on a rotary evaporator The excess 1,6-dibromohexane was removed a wiped film evaporator the resulting crude product chromatographed on silica (5 kg Biotage) eluting with 5% ethyl acetate in petrol 60/80

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Sodium methoxide (104.4 g, 1.93 mol) was added portionwise to ethylene glycol (3.74 L) under N2, keeping the temperature below 35° C. After 1–2 h, 2,6-dichlorobenzylbromide (400 g, 1.67 mol) was added and the mixture heated to 55–60° C. for 1 h. On cooling to 20° C. water (2.14 L) was added and the mixture extracted with ethyl acetate (2.14 L). The aqueous layer was separated and extracted twice with ethyl acetate (2.14 L, 1.28 L). The combined organic extracts were washed with water (2.14 L) then evaporated to dryness to afford a colourless oil (371.8 g)—LC RT=4 min. This may be chromatographed on silica (Biotage) eluting with 10% ethyl acetate in 60/80 petrol to afford the title compound. the temperature below 35° C After 1–2 h the mixture heated to 55–60° C. for 1 h was added the mixture extracted with ethyl acetate (2.14 L) The aqueous layer was separated extracted twice with ethyl acetate (2.14 L, 1.28 L) The combined organic extracts were washed with water (2.14 L) then evaporated to dryness

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 50% aq NaOH (1.89 L), 2-(2,6-dichlorobenzyloxy)ethanol (473.2 g), 1,6-dibromohexane (2.44 kg, 5 eq) and tetrabutylammonium bromide (34.1 g, 5 mol %) in toluene (1.89 L) was heated to 55-60° C. for 8-20 h. On cooling water (558 mL) and toluene (558 mL) were added. The aqueous phase was separated and diluted with water (1 L) then back extracted with toluene (1.1 L). The combined toluene extracts were washed twice with water (2.2 L), then evaporated to dryness on a rotary evaporator. The excess 1,6-dibromohexane was removed using a wiped film evaporator, and the resulting crude product chromatographed on silica (5 kg Biotage), eluting with 5% ethyl acetate in petrol 60/80, to give the title compound (503.2 g)−LC RT=7.0 min. were added The aqueous phase was separated diluted with water (1 L) then back extracted with toluene (1.1 L) The combined toluene extracts were washed twice with water (2.2 L) evaporated to dryness on a rotary evaporator The excess 1,6-dibromohexane was removed a wiped film evaporator the resulting crude product chromatographed on silica (5 kg Biotage) eluting with 5% ethyl acetate in petrol 60/80

反応条件: temp:57.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Sodium methoxide (104.4 g, 1.93 mol) was added portionwise to ethylene glycol (3.74 L) under N2, keeping the temperature below 35° C. After 1-2 h, 2,6-dichlorobenzylbromide (400 g, 1.67 mol) was added and the mixture heated to 55-60° C. for 1 h. On cooling to 20° C. water (2.14 L) was added and the mixture extracted with ethyl acetate (2.14 L). The aqueous layer was separated and extracted twice with ethyl acetate (2.14 L, 1.28 L). The combined organic extracts were washed with water (2.14 L) then evaporated to dryness to afford a colourless oil (371.8 g)−LC RT=4 min. This may be chromatographed on silica (Biotage) eluting with 10% ethyl acetate in 60/80 petrol to afford the title compound. the temperature below 35° C was added the mixture extracted with ethyl acetate (2.14 L) The aqueous layer was separated extracted twice with ethyl acetate (2.14 L, 1.28 L) The combined organic extracts were washed with water (2.14 L) then evaporated to dryness

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 50% aq NaOH (1.89 L), 2-(2,6-dichlorobenzyloxy)ethanol (473.2 g), 1,6-dibromohexane (2.44 kg, 5 eq) and tetrabutylammonium bromide (34.1 g, 5 mol %) in toluene (1.89 L) was heated to 55-60° C. for 8-20 h. On cooling water (558 mL) and toluene (558 mL) were added. The aqueous phase was separated and diluted with water (1 L) then back extracted with toluene (1.1 L). The combined toluene extracts were washed twice with water (2.2 L), then evaporated to dryness on a rotary evaporator. The excess 1,6-dibromohexane was removed using a wiped film evaporator, and the resulting crude product chromatographed on silica (5 kg Biotage), eluting with 5% ethyl acetate in petrol 60/80, to give the title compound (503.2 g)-LC RT=7.0 min. were added The aqueous phase was separated diluted with water (1 L) then back extracted with toluene (1.1 L) The combined toluene extracts were washed twice with water (2.2 L) evaporated to dryness on a rotary evaporator The excess 1,6-dibromohexane was removed a wiped film evaporator the resulting crude product chromatographed on silica (5 kg Biotage) eluting with 5% ethyl acetate in petrol 60/80

反応条件: temp:57.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Sodium methoxide (104.4 g, 1.93 mol) was added portionwise to ethylene glycol (3.74 L) under N2, keeping the temperature below 35° C. After 1-2 h, 2,6-dichlorobenzylbromide (400 g, 1.67 mol) was added and the mixture heated to 55-60° C. for 1 h. On cooling to 20° C. water (2.14 L) was added and the mixture extracted with ethyl acetate (2.14 L). The aqueous layer was separated and extracted twice with ethyl acetate (2.14 L, 1.28 L). The combined organic extracts were washed with water (2.14 L) then evaporated to dryness to afford a colourless oil (371.8 g)-LC RT=4 min. This may be chromatographed on silica (Biotage) eluting with 10% ethyl acetate in 60/80 petrol to afford the title compound. the temperature below 35° C was added the mixture extracted with ethyl acetate (2.14 L) The aqueous layer was separated extracted twice with ethyl acetate (2.14 L, 1.28 L) The combined organic extracts were washed with water (2.14 L) then evaporated to dryness