2-(3-氨基氧杂环丁烷-3-基)乙酸乙酯

反应条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Ethyl oxetan-3-ylideneacetate (Preparation 38, 781 g, 5.49 mol) was dissolved in 2M ammonia in ethanol (8.24 L) and heated to 100° C. in a bomb for 5 hours. The reaction was concentrated in vacuo to afford the title compound as a mobile oil (750 g, 100% yield). The reaction was concentrated in vacuo

反应条件: temp:5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: tert-Butyl methyl ether (2.5 L) and an aqueous solution of sodium carbonate (750 g in 2.2 L water, 7.07 mol) were stirred. Ethyl (3-aminooxetan-3-yl)acetate (Preparation 30, 875 g, 5.5 mol) was added to the reaction followed by further tert-butyl methyl ether (2.5 L). The reaction was cooled to 5° C. and benzyl chloroformate (1.21 Kg, 7.09 mol) added in a controlled manner such as to maintain the temperature below 20° C. A precipitate was observed so further water (5 L) and tert-butyl methyl ether (1.5 L) were added to solubilise the reaction mixture. The biphasic mixture was separated. The organic layer was basified with 2M aqueous solution of sodium hydroxide (3.5 L) and stirred vigorously for 18 hours. The aqueous layer was separated and the remaining organic layer washed with water (1.5 L). The aqueous layers were combined and cooled to 15° C. Isopropyl acetate (5 L) was added followed by controlled addition of a 6M aqueous solution of hydrogen chloride (1.2 L), maintaining the temperature below 17° C. The reaction was stirred for 30 minutes. Solid crystallised out in the reactor so was dissolved in a mixture of ethyl acetate and methanol (˜20 L). The solution was stirred at room temperature for 18 hours. The reaction was concentrated in vacuo to afford solid material. Ethyl acetate (5 L) was added and concentrated in vacuo. Further ethyl acetate (5 L) was added and the slurry heated to reflux to give an orange solution. The solution was cooled to 50° C. and heptane (2.5 L) added. A thick slurry was observed that was stirred at room temperature for 18 hours. The solid was filtered and dried on a sinter for 3 hours before drying in vacuo at 40° C. for 18 hours to afford the title compound as a white crystalline solid (1.07 Kg, 73% yield). to maintain the temperature below 20° C were added The biphasic mixture was separated The aqueous layer was separated the remaining organic layer washed with water (1.5 L) cooled to 15° C Isopropyl acetate (5 L) was added followed by controlled addition of a 6M aqueous solution of hydrogen chloride (1.2 L) maintaining the temperature below 17° C The reaction was stirred for 30 minutes Solid crystallised out in the reactor so was dissolved in a mixture of ethyl acetate and methanol (˜20 L) The solution was stirred at room temperature for 18 hours The reaction was concentrated in vacuo to afford solid material concentrated in vacuo Further ethyl acetate (5 L) was added the slurry heated to reflux to give an orange solution The solution was cooled to 50° C. that was stirred at room temperature for 18 hours The solid was filtered dried on a sinter for 3 hours before drying in vacuo at 40° C. for 18 hours

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of (3-Amino-oxetan-3-yl)-acetic acid ethyl ester (CAN 1207175-54-9, 0.3 g, 1.88 mmol) in methanamine 41% aqueous solution (1.86 g, 2.09 ml, 24.5 mmol) was stirred overnight at 60° C. The reaction was evaporated down to dryness and to yield the title compound (278 mg, 102%) as a crude solid which was used without any purification. MS (ESI, m/z): 145.2 (M+H+). The reaction was evaporated down to dryness

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: In a microwave tube was added ethyl 2-(3-aminooxetan-3-yl)acetate (CAN 1207175-54-9, 470 mg, 2.95 mmol). Toluene (7.0 ml) and 40%-dimethylamine solution in water (8.9 g, 10.0 ml, 79.0 mmol) were added. The tube was sealed and the reaction mixture was stirred vigorously at room temperature for 7 days. The reaction mixture was concentrated in vacuo and azeotroped several times with 30 mL toluene. The crude solid was dried under high vacuum at 40° C. for 3 hours to yield the title compound (405 mg, 87%). MS (ESI, m/z): 159.1 (M+H+). The tube was sealed The reaction mixture was concentrated in vacuo azeotroped several times with 30 mL toluene The crude solid was dried under high vacuum at 40° C. for 3 hours

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a microwave tube was added ethyl 2-(3-aminooxetan-3-yl)acetate (CAN 1207175-54-9, 400 mg, 2.51 mmol) followed by toluene (8.0 ml) and 25% ammonium hydroxide (7.2 g, 8.0 ml, 51.4 mmol). The tube was sealed and the reaction mixture was stirred vigorously at room temperature for 6 days. The reaction mixture was concentrated in vacuo and azeotroped several times with 20 ml toluene. The crude solid was dried under high-vacuum at 40° C. to dryness to yield the title compound (290 mg, 89%) as a white solid. MS (ESI, m/z): 131.1 (M+H+). The tube was sealed The reaction mixture was concentrated in vacuo azeotroped several times with 20 ml toluene The crude solid was dried under high-vacuum at 40° C. to dryness