ethyl 2-(4-benzylmorpholin-2-yl)acetate

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:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2-(Benzylamino)ethanol (19.05 ml, 132 mmol) and triethylamine (18.44 ml, 132 mmol) was added to water (150 ml) and the resulting mixture was heated to reflux temperature. (E)-Ethyl 4-bromobut-2-enoate (18.24 ml, 132 mmol) was added dropwise for 10 min The resulting mixture was further maintained at reflux temperature for 5 h. The reaction mixture was cooled to 25° C. and added NaOH (5.29 g, 132 mmol) after that the solvent was removed by distillation under reduced pressure to give orange oil. Ethyl acetate (150 mL) was added and the resulting solution was washed with water (2×50 mL). Ethyl acetate was distilled off under reduced pressure to give crude compound (15 g). This crude compound was purified by flash chromatography (Biotage) using eluent 20% ethyl acetate in hexane to yield 13 g of pure title compound as colorless viscous oil. m/z 264.08. the resulting mixture was heated to reflux temperature was further maintained at reflux temperature for 5 h was removed by distillation under reduced pressure to give orange oil the resulting solution was washed with water (2×50 mL) Ethyl acetate was distilled off under reduced pressure to give crude compound (15 g) This crude compound was purified by flash chromatography (Biotage)

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 2-ethoxycarbonylmethyl-4-benzylmorpholine (41 g) in diethyl ether (100 ml) is added dropwise to a stirred suspension of lithium aluminum hydride (59.2 g) in diethyl ether (150 ml). The reaction mixture is stirred at 25° C. for 1 hour. The excess of lithium aluminum hydride is decomposed by the successive addition of ethyl acetate and water. The insoluble materials are filtered off, and the filtrate is evaporated to give the title compound (34.4 g) as an oil. The starting material, 2-ethoxycarbonylmethyl-4-benzylmorpholine, is prepared according to the method of F. Loftus [Syn. Commun., 10, 59-73 (1980)]. The insoluble materials are filtered off the filtrate is evaporated

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

実験手順: To a refluxing mixture of 15 parts of lithium aluminum hydride and 534 parts of tetrahydrofuran was added dropwise a solution of 80 parts of ethyl 4-(phenylmethyl)-2-morpholineacetate (described in C.A.; 93, 26362g) in 89 parts of tetrahydrofuran under a nitrogen atmosphere. Refluxing was continued overnight. After cooling to 0°-5° C., there were added successively 15.6 parts of water, 14.6 parts of NaOH 20% and 51 parts of water. The whole was stirred for 1/2 hour and then filtered over diatomaceous earth. The filtrate was evaporated, yielding 68 parts (99.1%) of 4-(phenylmethyl)-2-morpholineethanol (interm. 4). Refluxing After cooling to 0°-5° C. filtered over diatomaceous earth The filtrate was evaporated

反応条件: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2-(Benzylamino)ethanol (19.05 ml, 132 mmol) and triethylamine (18.44 ml, 132 mmol) was added to water (150 ml) and the resulting mixture was heated to reflux temperature. (E)-Ethyl 4-bromobut-2-enoate (18.24 ml, 132 mmol) was added dropwise for 10 min The resulting mixture was further maintained at reflux temperature for 5 h. The reaction mixture was cooled to 25° C. and added NaOH (5.29 g, 132 mmol) after that the solvent was removed by distillation under reduced pressure to give orange oil. Ethyl acetate (150 mL) was added and the resulting solution was washed with water (2×50 mL). Ethyl acetate was distilled off under reduced pressure to give crude compound (15 g). This crude compound was purified by flash chromatography (Biotage) using eluent 20% ethyl acetate in hexane to yield 13 g of pure title compound as colorless viscous oil. m/z 264.08. the resulting mixture was heated to reflux temperature was further maintained at reflux temperature for 5 h was removed by distillation under reduced pressure to give orange oil the resulting solution was washed with water (2×50 mL) Ethyl acetate was distilled off under reduced pressure to give crude compound (15 g) This crude compound was purified by flash chromatography (Biotage)