morpholine-3,5-dione

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:; See reaction.notes.procedure_details.

Procedure: 1.0 g 2-[1-(chloroacetyl)piperidin-4-yl]-5-(3,4-dimethoxyphenyl)-4,4-dimethyl-2,4-dihydro-3H-pyrazol-3-one (compound A1), 0.5 g morpholine-3,5-dione and 1.0 g K2CO3 in 20 ml of DMF is heated for 17 h at 80-100° C. The DMF is removed in vacuo and the residue dissolved in 70 ml of DCM, washed four times with 30 ml of water and 20 ml of 0.5 M H2SO4. The DCM layer is dried over MgSO4 and concentrated in vacuo. The title product is crystallized from diethyl ether. The DMF is removed in vacuo the residue dissolved in 70 ml of DCM washed four times with 30 ml of water and 20 ml of 0.5 M H2SO4 The DCM layer is dried over MgSO4 concentrated in vacuo The title product is crystallized from diethyl ether

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

Procedure: 1.0 g 2-[1-(chloroacetyl)piperidin-4-yl]-5-(3,4-dimethoxyphenyl)-4,4-dimethyl-2,4-dihydro-3H-pyrazol-3-one (compound A1), 0.5 g morpholine-3,5-dione and 1.0 g K2CO3 in 20 ml of DMF is heated for 17 h at 80-100° C. The DMF is removed in vacuo and the residue dissolved in 70 ml of DCM, washed four times with 30 ml of water and 20 ml of 0.5 M H2SO4. The DCM layer is dried over MgSO4 and concentrated in vacuo. The title product is crystallized from diethyl ether. The DMF is removed in vacuo the residue dissolved in 70 ml of DCM washed four times with 30 ml of water and 20 ml of 0.5 M H2SO4 The DCM layer is dried over MgSO4 concentrated in vacuo The title product is crystallized from diethyl ether

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: To a suspension of sodium hydride (480 mg, 60% in mineral oil, 12 mmol) in 10 ml of anhydrous THF is added morpholine-3,5-dione (1.2 g, 10 mmol) in 20 ml of THF under an argon athmosphere. After 10 min., 1-carbethoxycyclopropyltriphenylphosphonium tetrafluoroborate (Fuchs' reagent, 6.8 g, 11 mmol)) in 20 ml of THF are added and the mixture is refluxed for 21 hours. After cooling, the suspension is concentrated on a rotary evaporator, poured onto ice/sat. sodium bicarbonate solution, and extracted three times with ether. The combined organic phases are washed with brine, dried over anhydrous sodium sulphate, and evaporated. The residual yellow oil (3.04 g) is purified by chromatography (Silica gel 60, 0.063-0.2 mesh, cyclohexane/ethyl acetate 1:1). the mixture is refluxed for 21 hours After cooling the suspension is concentrated on a rotary evaporator poured onto ice/ sodium bicarbonate solution, and extracted three times with ether The combined organic phases are washed with brine dried over anhydrous sodium sulphate evaporated The residual yellow oil (3.04 g) is purified by chromatography (Silica gel 60, 0.063-0.2 mesh, cyclohexane/ethyl acetate 1:1)

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

Procedure: To a suspension of sodium hydride (480 mg, 60% in mineral oil, 12 mmol) in 10 ml of anhydrous THF is added morpholine-3,5-dione (1.2 g, 10 mmol) in 20 ml of THF under an argon athmosphere. After 10 min., 1-carbethoxycyclopropyltriphenylphosphonium tetrafluoroborate (Fuchs' reagent, 6.8 g, 11 mmol)) in 20 ml of THF are added and the mixture is refluxed for 21 hours. After cooling, the suspension is concentrated on a rotary evaporator, poured onto ice/sat. sodium bicarbonate solution, and extracted three times with ether. The combined organic phases are washed with brine, dried over anhydrous sodium sulphate, and evaporated. The residual yellow oil (3.04 g) is purified by chromatography (Silica gel 60, 0.063-0.2 mesh, cyclohexane/ethyl acetate 1:1). the mixture is refluxed for 21 hours After cooling the suspension is concentrated on a rotary evaporator poured onto ice/ sodium bicarbonate solution, and extracted three times with ether The combined organic phases are washed with brine dried over anhydrous sodium sulphate evaporated The residual yellow oil (3.04 g) is purified by chromatography (Silica gel 60, 0.063-0.2 mesh, cyclohexane/ethyl acetate 1:1)

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

Procedure: A pale yellow suspension of morpholine-3,5-dione (1.2 g, 10 mmol), of 1,3-dibromopropane (3.4 ml, 33 mmol), and potassium carbonate (2.7 g, 19 mmol) in 23 ml of 2-butanone is refluxed under an argon athmosphere for 22 hours. After cooling, the suspension is concentrated on a rotary evaporator, poured into ice/water, and extracted twice with ethyl acetate. The combined organic phases are washed with brine, dried over anhydrous sodium sulphate, and evaporated. The residual yellow oil (2.06 g) is purified by chromatography (Biotage 40Mi, I=15 cm, cyclohexane/ethyl acetate 3:1). After cooling the suspension is concentrated on a rotary evaporator poured into ice/water extracted twice with ethyl acetate The combined organic phases are washed with brine dried over anhydrous sodium sulphate evaporated The residual yellow oil (2.06 g) is purified by chromatography (Biotage 40Mi, I=15 cm, cyclohexane/ethyl acetate 3:1)

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

Procedure: A pale yellow suspension of morpholine-3,5-dione (1.2 g, 10 mmol), of 1,3-dibromopropane (3.4 ml, 33 mmol), and potassium carbonate (2.7 g, 19 mmol) in 23 ml of 2-butanone is refluxed under an argon athmosphere for 22 hours. After cooling, the suspension is concentrated on a rotary evaporator, poured into ice/water, and extracted twice with ethyl acetate. The combined organic phases are washed with brine, dried over anhydrous sodium sulphate, and evaporated. The residual yellow oil (2.06 g) is purified by chromatography (Biotage 40Mi, I=15 cm, cyclohexane/ethyl acetate 3:1). After cooling the suspension is concentrated on a rotary evaporator poured into ice/water extracted twice with ethyl acetate The combined organic phases are washed with brine dried over anhydrous sodium sulphate evaporated The residual yellow oil (2.06 g) is purified by chromatography (Biotage 40Mi, I=15 cm, cyclohexane/ethyl acetate 3:1)