tert-butyl 2-morpholin-4-ylacetate

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

実験手順: Tert-butyl 2-morpholinoacetate (11 g, 54.7 mmol) was stirred with HCl, 4M in dioxane (54 mL), giving a white precipitate (a mild exotherm was observed) which slowly dissolved with stirring at room temperature. Ten minutes after complete dissolution, the mixture solidified. Then the mixture was warmed to 60° C. and the thick suspension was stirred vigorously overnight. The mixture was then cooled to room temperature, diluted with diethyl ether (60 mL) and filtered to collect the title compound (8 g, 80%) as a white solid. 1H NMR (CD3OD, 400 MHz): δ (ppm) 4.13 (s, 2H), 3.94 (brm, 4H), 3.41 (brm, 4H). giving a white precipitate (a mild exotherm slowly dissolved Ten minutes after complete dissolution Then the mixture was warmed to 60° C. the thick suspension was stirred vigorously overnight The mixture was then cooled to room temperature filtered to collect the title compound (8 g, 80%) as a white solid

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred solution of tert-butyl bromoacetate (8.47 mL, 57.4 mmol) in THF (50 mL) was added a 1:1 mixture of triethylamine (8 mL, 57.4 mmol) and morpholine (5.02 mL, 57.4 mmol), dropwise (a mild exotherm was observed) and the resulting white suspension was stirred at 60° C. for 2 h. The mixture was diluted with water (100 mL) and saturated sodium carbonate (50 mL) and extracted with ethyl acetate (2×50 mL). The combined organics were washed with saturated sodium carbonate (100 mL), water (3×50 mL), and brine (50 mL). The organic phase was dried over anhydrous sodium sulfate, filtered and concentrated then chromatographed in 0%-100% ethyl acetate in hexanes. Product-containing fractions were concentrated in vacuo giving the title product (11.5 g, quantitative) as a pale yellow liquid. 1H NMR (CDCl3, 400 MHz): δ (ppm) 3.78-3.71 (m, 4H), 3.10 (s, 2H), 2.59-2.54 (m, 4H), 1.46 (m, 9H). extracted with ethyl acetate (2×50 mL) The combined organics were washed with saturated sodium carbonate (100 mL), water (3×50 mL), and brine (50 mL) The organic phase was dried over anhydrous sodium sulfate filtered concentrated then chromatographed in 0%-100% ethyl acetate in hexanes Product-containing fractions were concentrated in vacuo

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

実験手順: Tert-butyl 2-morpholinoacetate (11 g, 54.7 mmol) was stirred with HCl, 4M in dioxane (54 mL), giving a white precipitate (a mild exotherm was observed) which slowly dissolved with stirring at room temperature. Ten minutes after complete dissolution, the mixture solidified. Then the mixture was warmed to 60° C. and the thick suspension was stirred vigorously overnight. The mixture was then cooled to room temperature, diluted with diethyl ether (60 mL) and filtered to collect the title compound (8 g, 80%) as a white solid. 1H NMR (CD3OD, 400 MHz): δ (ppm) 4.13 (s, 2H), 3.94 (brm, 4H), 3.41 (brm, 4H). giving a white precipitate (a mild exotherm slowly dissolved Ten minutes after complete dissolution Then the mixture was warmed to 60° C. the thick suspension was stirred vigorously overnight The mixture was then cooled to room temperature filtered to collect the title compound (8 g, 80%) as a white solid

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred solution of tert-butyl bromoacetate (8.47 mL, 57.4 mmol) in THF (50 mL) was added a 1:1 mixture of triethylamine (8 mL, 57.4 mmol) and morpholine (5.02 mL, 57.4 mmol), dropwise (a mild exotherm was observed) and the resulting white suspension was stirred at 60° C. for 2 h. The mixture was diluted with water (100 mL) and saturated sodium carbonate (50 mL) and extracted with ethyl acetate (2×50 mL). The combined organics were washed with saturated sodium carbonate (100 mL), water (3×50 mL), and brine (50 mL). The organic phase was dried over anhydrous sodium sulfate, filtered and concentrated then chromatographed in 0%-100% ethyl acetate in hexanes. Product-containing fractions were concentrated in vacuo giving the title product (11.5 g, quantitative) as a pale yellow liquid. 1H NMR (CDCl3, 400 MHz): δ (ppm) 3.78-3.71 (m, 4H), 3.10 (s, 2H), 2.59-2.54 (m, 4H), 1.46 (m, 9H). extracted with ethyl acetate (2×50 mL) The combined organics were washed with saturated sodium carbonate (100 mL), water (3×50 mL), and brine (50 mL) The organic phase was dried over anhydrous sodium sulfate filtered concentrated then chromatographed in 0%-100% ethyl acetate in hexanes Product-containing fractions were concentrated in vacuo

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

実験手順: To a stirred solution of tert-butyl bromoacetate (1.61 mL, 10.0 mmol) in THF (25 mL) was added morpholine (1.74 mL, 20.0 mmol); the resultant suspension was stirred for 1.5 h and then concentrated. The residue was dissolved in CH2Cl2 (50 mL)/saturated Na2CO3 (75 mL), the layers were separated, and the aqueous layer was extracted with additional CH2Cl2 (2×25 mL). The combined organics were washed with saturated Na2CO3 (20 mL) and brine (30 mL), dried and concentrated to give crude title compound. Tituration with EtOAc (15 mL), filtration, and concentration of the filtrate gave the title compound (2.01 g, 100%) as a colorless oil. TLC: Rf 0.45 (EtOAc). 1H NMR: δ3.79-3.73 (m, 4H, CH2OCH2), 3.11 (s, 2H, CH2), 2.61-2.55 (m, 4H, CH2NCH2), 1.46 (s, 9H, t-Bu). MS (DCI/CH4): m/z (rel intensity) 202 (MH+, 15), 201 (8), 200 (13), 174 (20), 146 (100), 100 (23). HRMS (C10H19NO3) (MH+): calcd, 201.1365; obsd, 201.1371. concentrated The residue was dissolved in CH2Cl2 (50 mL)/saturated Na2CO3 (75 mL) the layers were separated the aqueous layer was extracted with additional CH2Cl2 (2×25 mL) The combined organics were washed with saturated Na2CO3 (20 mL) and brine (30 mL) dried concentrated to give crude title compound Tituration with EtOAc (15 mL), filtration, and concentration of the filtrate

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

実験手順: Tert-butyl 2-morpholinoacetate (11 g, 54.7 mmol) was stirred with HCl, 4M in dioxane (54 mL), giving a white precipitate (a mild exotherm was observed) which slowly dissolved with stirring at room temperature. Ten minutes after complete dissolution, the mixture solidified. Then the mixture was warmed to 60° C. and the thick suspension was stirred vigorously overnight. The mixture was then cooled to room temperature, diluted with diethyl ether (60 mL) and filtered to collect the title compound (8 g, 80%) as a white solid. 1H NMR (CD3OD, 400 MHz): δ (ppm) 4.13 (s, 2H), 3.94 (brm, 4H), 3.41 (brm, 4H). giving a white precipitate (a mild exotherm slowly dissolved Ten minutes after complete dissolution Then the mixture was warmed to 60° C. the thick suspension was stirred vigorously overnight The mixture was then cooled to room temperature filtered to collect the title compound (8 g, 80%) as a white solid

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred solution of tert-butyl bromoacetate (8.47 mL, 57.4 mmol) in THF (50 mL) was added a 1:1 mixture of triethylamine (8 mL, 57.4 mmol) and morpholine (5.02 mL, 57.4 mmol), dropwise (a mild exotherm was observed) and the resulting white suspension was stirred at 60° C. for 2 h. The mixture was diluted with water (100 mL) and saturated sodium carbonate (50 mL) and extracted with ethyl acetate (2×50 mL). The combined organics were washed with saturated sodium carbonate (100 mL), water (3×50 mL), and brine (50 mL). The organic phase was dried over anhydrous sodium sulfate, filtered and concentrated then chromatographed in 0%-100% ethyl acetate in hexanes. Product-containing fractions were concentrated in vacuo giving the title product (11.5 g, quantitative) as a pale yellow liquid. 1H NMR (CDCl3, 400 MHz): δ (ppm) 3.78-3.71 (m, 4H), 3.10 (s, 2H), 2.59-2.54 (m, 4H), 1.46 (m, 9H). extracted with ethyl acetate (2×50 mL) The combined organics were washed with saturated sodium carbonate (100 mL), water (3×50 mL), and brine (50 mL) The organic phase was dried over anhydrous sodium sulfate filtered concentrated then chromatographed in 0%-100% ethyl acetate in hexanes Product-containing fractions were concentrated in vacuo