methyl 2-morpholin-4-ylacetate

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:95.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: In a 25 mL, sealed tube, methyl 2-morpholinoacetate (0.5 g, 1.0 eq.) was dissolved in ethanol (5 mL) at RT. Methylhydrazine (0.16 g, 1.1 eq.) was introduced dropwise at RT and the reaction mixture was refluxed at 95° C. for 48 h. The reaction mixture was concentrated under reduced pressure (40° C., 20 mm Hg) to afford the crude N-methyl-2-morpholinoacetohydrazide (0.27 g) which was used without further purification in the following step. In a 25 mL, sealed tube The reaction mixture was concentrated under reduced pressure (40° C., 20 mm Hg)

反応条件: temp:95.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: In a 25 mL, 3-neck round-bottom flask, methyl 2-morpholinoacetate (0.25 g, 1.0 eq.) was dissolved in ethanol (5 mL) at RT. Hydrazine hydrate (0.087 g, 1.1 eq.) was introduced dropwise at RT and the reaction mixture was refluxed at 95° C. for 20 h. The reaction mixture was concentrated under reduced pressure (40° C., 20 mm Hg) to afford the crude 2-morpholinoacetohydrazide (0.23 g) which was used without further purification in the following step. The reaction mixture was concentrated under reduced pressure (40° C., 20 mm Hg)

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 methyl 2-morpholin-4-ylacetate (1.0 g, 6.28 mmol) in 1 mL of anhydrous ethanol was added anhydrous hydrazine (0.305 mL, 6.28 mmol). The solution was heated to reflux temperature overnight. The solvent was then removed under reduced pressure and the product was isolated as a solid in a quantitative yield and was used without further purification: 1H NMR (CDCl3) δ8.11 (br s, 1H), 3.87 (br s, 2H), 3.71 (t, 4H), 3.09 (s, 6H), 2.53 (t, 4H); ES-MS (m/z) 160 [M+H]+. The solution was heated to reflux temperature overnight The solvent was then removed under reduced pressure the product was isolated as a solid in a quantitative yield was used without further purification

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

実験手順: 2',3'-Dihydroxy-acetophenone (7.5 g, 49 mmole) is dissolved in 303 ml dry tetrahydrofuran in a flame dried 1,000 ml three neck round bottom flask under nitrogen. The solution is treated rapidly dropwise with potassium t-butoxide (1.0 M/THF) (197 ml, 197 mmole) and is mechanically stirred vigorously as methyl-2-(4-morpholinyl)-acetate (10.2 g, 64 mmole) is added neat. The reaction mixture is heated at reflux for 48 h, is treated with a second lot of methyl-2-(4-morpholinyl)-acetate (7 g, 44 mmole), and is stirred an additional 24h at reflux. The reaction is cooled to room temperature, is diluted with 200 ml water, and the tetrahydrofuran is removed in vacuo. The pH of the aqueous residue is adjusted to 6.8 with 10% hydrochloric acid and the mixture is extracted with 5×100 ml dichloromethane. The combined organics are dried over magnesium sulfate and are concentrated in vacuo to a brown solid. The solid is washed with 200 ml diethyl ether and is dried to afford 8.8 g of a tan solid. The solid is recrystallized twice from ethyl acetate to provide 7.5 g (60%) of the title compound as an off-white solid, mp. 202.5° C. dried 1,000 ml three neck round bottom flask under nitrogen is added neat The reaction mixture is heated at reflux for 48 h at reflux the tetrahydrofuran is removed in vacuo the mixture is extracted with 5×100 ml dichloromethane The combined organics are dried over magnesium sulfate are concentrated in vacuo to a brown solid The solid is washed with 200 ml diethyl ether is dried

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

実験手順: As described for example 112a, morpholin-4-yl-acetic acid methyl ester in butanol was reacted with hydrazine hydrate (1.2 equivalents) at 100° C. for 1 h. Evaporation of all volatiles and crystallization from n-butanol/toluene afforded the title compound as a white solid (yield: 68%). 1H-NMR (300 MHz, DMSO): δ=2.40 (m, 4H), 2.90 (s, 2H), 3.57 (m, 4H), 4.24 (s, 2H), 8.91 (s, 1H). Evaporation of all volatiles and crystallization from n-butanol/toluene

反応条件: temp:95.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: In a 25 mL, sealed tube, methyl 2-morpholinoacetate (0.5 g, 1.0 eq.) was dissolved in ethanol (5 mL) at RT. Methylhydrazine (0.16 g, 1.1 eq.) was introduced dropwise at RT and the reaction mixture was refluxed at 95° C. for 48 h. The reaction mixture was concentrated under reduced pressure (40° C., 20 mm Hg) to afford the crude N-methyl-2-morpholinoacetohydrazide (0.27 g) which was used without further purification in the following step. In a 25 mL, sealed tube The reaction mixture was concentrated under reduced pressure (40° C., 20 mm Hg)

反応条件: temp:95.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: In a 25 mL, 3-neck round-bottom flask, methyl 2-morpholinoacetate (0.25 g, 1.0 eq.) was dissolved in ethanol (5 mL) at RT. Hydrazine hydrate (0.087 g, 1.1 eq.) was introduced dropwise at RT and the reaction mixture was refluxed at 95° C. for 20 h. The reaction mixture was concentrated under reduced pressure (40° C., 20 mm Hg) to afford the crude 2-morpholinoacetohydrazide (0.23 g) which was used without further purification in the following step. The reaction mixture was concentrated under reduced pressure (40° C., 20 mm Hg)

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

実験手順: A solution of methyl N-morpholinoacetate (0.85 g, 5.3 mmol) in 1:1 5N NaOH/THF (10 ml) was stirred at 50° C. for 1 h then neutralized to pH 3 with 6N HCl and concentrated. The yellowish solid was diluted with 1:1 MeOH/CH2Cl2 (25 ml), filtered to remove inorganic salts, and concentrated. The dilution, filtration and concentration were repeated to give morpholin-4-yl-acetic acid (695 mg, 90%) as a yellow solid. concentrated The yellowish solid was diluted with 1:1 MeOH/CH2Cl2 (25 ml) filtered to remove inorganic salts concentrated The dilution, filtration and concentration

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

実験手順: To a solution of methyl 2-morpholin-4-ylacetate (1.0 g, 6.28 mmol) in 1 mL of anhydrous ethanol was added anhydrous hydrazine (0.305 mL, 6.28 mmol). The solution was heated to reflux temperature overnight. The solvent was then removed under reduced pressure and the product was isolated as a solid in a quantitative yield and was used without further purification: 1H NMR (CDCl3) δ 8.11 (br s, 1H), 3.87 (br s, 2H), 3.71 (t, 4H), 3.09 (s, 6H), 2.53 (t, 4H); ES-MS (m/z) 160 [M+H]+. The solution was heated to reflux temperature overnight The solvent was then removed under reduced pressure the product was isolated as a solid in a quantitative yield was used without further purification

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

実験手順: To a solution of methyl 2-morpholin-4-ylacetate (1.0 g, 6.28 mmol) in 1 mL of anhydrous ethanol was added anhydrous hydrazine (0.305 mL, 6.28 mmol). The solution was heated to reflux temperature overnight. The solvent was then removed under reduced pressure and the product was isolated as a solid in a quantitative yield and was used without further purification: 1H NMR (CDCl3) δ8.11 (br s, 1H), 3.87 (br s, 2H), 3.71 (t, 4H), 3.09 (s, 6H), 2.53 (t, 4H); ES-MS (m/z) 160 [M+H]+. The solution was heated to reflux temperature overnight The solvent was then removed under reduced pressure the product was isolated as a solid in a quantitative yield was used without further purification