4-chloromorpholine

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:16.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: N-chloromorpholine (24 g) in diethyl ether (20 ml) was added drop-wise over 2.5 h to a vigorously stirred solution of potassium hydroxide (22.1 g, 0.37 mol) in ethanol (130 ml) at 90° C. Heating was continued at 80° C. for 2 h. After standing at room temperature for 48 h the mixture was filtered to remove the inorganics and the solvent removed from the filtrate in vacuo. The residue was partitioned between diethyl ether and brine, dried (Na2SO4) and the solvent removed in vacuo. The resulting brown oil was dissolved in acetonitrile (100 ml). Triethylamine (25 ml) and monoethyl malonate (25 g) were added and the mixture heated at 16° C. for 16 h. The volatiles were removed in vacuo and the residue partitioned between saturated aqueous potassium carbonate and diethyl ether. The organic phase was dried (Na2SO4) and the solvent removed in vacuo to afford the title compound as a brown oil (3.5 g). Heating After standing at room temperature for 48 h the mixture was filtered to remove the inorganics the solvent removed from the filtrate in vacuo The residue was partitioned between diethyl ether and brine dried (Na2SO4) the solvent removed in vacuo The resulting brown oil was dissolved in acetonitrile (100 ml) Triethylamine (25 ml) and monoethyl malonate (25 g) were added The volatiles were removed in vacuo the residue partitioned between saturated aqueous potassium carbonate and diethyl ether The organic phase was dried (Na2SO4) the solvent removed in vacuo

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

Conditions: temp:16.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: N-chloromorpholine (24 g) in diethyl ether (20 ml) was added drop-wise over 2.5 h to a vigorously stirred solution of potassium hydroxide (22.1 g, 0.37 mol) in ethanol (130 ml) at 90° C. Heating was continued at 80° C. for 2 h. After standing at room temperature for 48 h the mixture was filtered to remove the inorganics and the solvent removed from the filtrate in vacuo. The residue was partitioned between diethyl ether and brine, dried (Na2SO4) and the solvent removed in vacuo. The resulting brown oil was dissolved in acetonitrile (100 ml). Triethylamine (25 ml) and monoethyl malonate (25 g) were added and the mixture heated at 16° C. for 16 h. The volatiles were removed in vacuo and the residue partitioned between saturated aqueous potassium carbonate and diethyl ether. The organic phase was dried (Na2SO4) and the solvent removed in vacuo to afford the title compound as a brown oil (3.5 g). Heating After standing at room temperature for 48 h the mixture was filtered to remove the inorganics the solvent removed from the filtrate in vacuo The residue was partitioned between diethyl ether and brine dried (Na2SO4) the solvent removed in vacuo The resulting brown oil was dissolved in acetonitrile (100 ml) Triethylamine (25 ml) and monoethyl malonate (25 g) were added The volatiles were removed in vacuo the residue partitioned between saturated aqueous potassium carbonate and diethyl ether The organic phase was dried (Na2SO4) the solvent removed in vacuo

Conditions: temp:16.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: N-chloromorpholine (24 g) in diethyl ether (20 ml) was added drop-wise over 2.5 h to a vigorously stirred solution of potassium hydroxide (22.1 g, 0.37 mol) in ethanol (130 ml) at 90° C. Heating was continued at 80° C. for 2 h. After standing at room temperature for 48 h the mixture was filtered to remove the inorganics and the solvent removed from the filtrate in vacuo. The residue was partitioned between diethyl ether and brine, dried (Na2SO4) and the solvent removed in vacuo. The resulting brown oil was dissolved in acetonitrile (100 ml). Triethylamine (25 ml) and monoethyl malonate (25 g) were added and the mixture heated at 16° C. for 16 h. The volatiles were removed in vacuo and the residue partitioned between saturated aqueous potassium carbonate and diethyl ether. The organic phase was dried (Na2SO4) and the solvent removed in vacuo to afford the title compound as a brown oil (3.5 g). Heating After standing at room temperature for 48 h the mixture was filtered to remove the inorganics the solvent removed from the filtrate in vacuo The residue was partitioned between diethyl ether and brine dried (Na2SO4) the solvent removed in vacuo The resulting brown oil was dissolved in acetonitrile (100 ml) Triethylamine (25 ml) and monoethyl malonate (25 g) were added The volatiles were removed in vacuo the residue partitioned between saturated aqueous potassium carbonate and diethyl ether The organic phase was dried (Na2SO4) the solvent removed in vacuo

Conditions: temp:16.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: N-chloromorpholine (24 g) in diethyl ether (20 ml) was added drop-wise over 2.5 h to a vigorously stirred solution of potassium hydroxide (22.1 g, 0.37 mol) in ethanol (130 ml) at 90° C. Heating was continued at 80° C. for 2 h. After standing at room temperature for 48 h the mixture was filtered to remove the inorganics and the solvent removed from the filtrate in vacuo. The residue was partitioned between diethyl ether and brine, dried (Na2SO4) and the solvent removed in vacuo. The resulting brown oil was dissolved in acetonitrile (100 ml). Triethylamine (25 ml) and monoethyl malonate (25 g) were added and the mixture heated at 16° C. for 16 h. The volatiles were removed in vacuo and the residue partitioned between saturated aqueous potassium carbonate and diethyl ether. The organic phase was dried (Na2SO4) and the solvent removed in vacuo to afford the title compound as a brown oil (3.5 g). Heating After standing at room temperature for 48 h the mixture was filtered to remove the inorganics the solvent removed from the filtrate in vacuo The residue was partitioned between diethyl ether and brine dried (Na2SO4) the solvent removed in vacuo The resulting brown oil was dissolved in acetonitrile (100 ml) Triethylamine (25 ml) and monoethyl malonate (25 g) were added The volatiles were removed in vacuo the residue partitioned between saturated aqueous potassium carbonate and diethyl ether The organic phase was dried (Na2SO4) the solvent removed in vacuo

Conditions: temp:16.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: N-chloromorpholine (24 g) in diethyl ether (20 ml) was added drop-wise over 2.5 h to a vigorously stirred solution of potassium hydroxide (22.1 g, 0.37 mol) in ethanol (130 ml) at 90° C. Heating was continued at 80° C. for 2 h. After standing at room temperature for 48 h the mixture was filtered to remove the inorganics and the solvent removed from the filtrate in vacuo. The residue was partitioned between diethyl ether and brine, dried (Na2SO4) and the solvent removed in vacuo. The resulting brown oil was dissolved in acetonitrile (100 ml). Triethylamine (25 ml) and monoethyl malonate (25 g) were added and the mixture heated at 16° C. for 16 h. The volatiles were removed in vacuo and the residue partitioned between saturated aqueous potassium carbonate and diethyl ether. The organic phase was dried (Na2SO4) and the solvent removed in vacuo to afford the title compound as a brown oil (3.5 g). Heating After standing at room temperature for 48 h the mixture was filtered to remove the inorganics the solvent removed from the filtrate in vacuo The residue was partitioned between diethyl ether and brine dried (Na2SO4) the solvent removed in vacuo The resulting brown oil was dissolved in acetonitrile (100 ml) Triethylamine (25 ml) and monoethyl malonate (25 g) were added The volatiles were removed in vacuo the residue partitioned between saturated aqueous potassium carbonate and diethyl ether The organic phase was dried (Na2SO4) the solvent removed in vacuo

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

Procedure: 4-n-Butyl-2-methoxybenzoic acid (0.5 g; 2.9 mmol) and N-chloromorpholine (356 mg; 2.9 mmol) were treated in a similar manner to that described in Preparation 24 to give the title compound as a white soid (0.4 g). described in Preparation 24

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

Procedure: To an ice cold solution of 4-chloro-2-methoxybenzoic acid (1.0 g, 5.36 mmol) in trifluoroacetic acid (7 ml) was added N-chloromorpholine (0.67 g, 5.5 mmol) dropwise, maintaining the internal temperature below 10° C. After stirring overnight at room temperature the trifluoroacetic acid was removed in vacuo and the residue partitioned between ethyl acethate and water. The organic layer was dried over magnesium sulfate, concentrated in vacuo and the residue recrystallised from methanol to afford the title compound as a white solid (200 mg). maintaining the internal temperature below 10° C was removed in vacuo the residue partitioned between ethyl acethate and water The organic layer was dried over magnesium sulfate concentrated in vacuo the residue recrystallised from methanol