ethyl 2-morpholin-3-ylacetate

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

実験手順: To a solution of monoethyl malonate (0.12 mol) and triethylamine (0.12 mol) acetonitrile (40 mL) and Step-1 intermediate was added (0.02 mol). The mixture was heated to a sufficient temperature to cause considerable evolution of CO2 gas. After 5 h, the solution was concentrated under reduced pressure. The residue was treated with 30% aqueous K2CO3 solution and extracted with diethyl ether, dried over Na2SO4 and concentrated to get the title compound. The mixture was heated to a sufficient temperature the solution was concentrated under reduced pressure The residue was treated with 30% aqueous K2CO3 solution extracted with diethyl ether dried over Na2SO4 concentrated

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

実験手順: To a solution of monoethyl malonate (0.12 mol) and triethylamine (0.12 mol) acetonitrile (40 mL) and Step-1 intermediate was added (0.02 mol). The mixture was heated to a sufficient temperature to cause considerable evolution of CO2 gas. After 5 h, the solution was concentrated under reduced pressure. The residue was treated with 30% aqueous K2CO3 solution and extracted with diethyl ether, dried over Na2SO4 and concentrated to get the title compound. The mixture was heated to a sufficient temperature the solution was concentrated under reduced pressure The residue was treated with 30% aqueous K2CO3 solution extracted with diethyl ether dried over Na2SO4 concentrated

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

実験手順: The title compound (1.48 g, 66%) was prepared from (RS)-morpholin-3-yl-acetic acid ethyl ester, D43 (1.37 g, 5.8 mmol) and 5-(4-fluoro-phenyl)-2-methyl-thiazole-4-carboxylic acid (1.00 g, 5.8 mmol) according to a procedure similar to that described for D16.

反応条件: temp:16.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 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

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

実験手順: Morpholin-3-ylacetic acid ethyl ester Chem Pharm Bull 94, 31(1), 1983 (2.10 g) was dissolved in dichloromethane (50 ml) and treated with triethylamine (1.33 g). The mixture was cooled (ice bath) and 5-(4-fluoro-phenyl)-2-methyl-thiazole-4-carbonyl chloride (1.53 g) in dichloromethane (10 ml) added. The mixture was stirred for 16 h, diluted with water and the organic phase separated. The aqueous phase was extracted with dichloromethane (2×100 ml), the organic phases combined, dried (Na2SO4) and solvent removed at reduced pressure. the residue was column chromatographed (silica gel, 40% ethyl acetate:pentane ˜60% ethyl acetate pentane eluant) to give the title compound (1.46 g). added the organic phase separated The aqueous phase was extracted with dichloromethane (2×100 ml) dried (Na2SO4) and solvent removed at reduced pressure chromatographed (silica gel, 40% ethyl acetate:pentane ˜60% ethyl acetate pentane eluant)

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

実験手順: The title compound (1.48 g, 66%) was prepared from (RS)-morpholin-3-yl-acetic acid ethyl ester, D43 (1.37 g, 5.8 mmol) and 5-(4-fluoro-phenyl)-2-methyl-thiazole4-carboxylic acid (1.00 g, 5.8 mmol) according to a procedure similar to that described for D16.

反応条件: temp:16.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 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

反応条件: temp:16.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 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