2-[(4-bromophenyl)methylamino]acetamide

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:; See reaction.notes.procedure_details.

実験手順: To a solution of 4-bromobenzaldehyde (100 g, 0.54 mol) and glycinamide hydrochloride (54 g, 0.48 mol) methanol/water (1500 ml, 5.5/1) was added sodium hydroxide (21.6 g, 0.54 mol). After stirring for 17 h at room temperature the reaction mixture was cooled to 0° C. Sodium borohydride (38 g, 1.0 mol) was added and the mixture was stirred until a clear solution was obtained. The reaction was quenched by addition of concentrated hydrochloric acid until pH=3. After stirring for 17 h the mixture was neutralized with a saturated aqueous solution of sodium hydrogen carbonate and the product was extracted into dichloromethane. The combined organic phases were washed with water, brine, dried over sodium sulfate and concentrated under reduced pressure to afford 2-(4-bromobenzylamino)acetamide (92 g). was cooled to 0° C the mixture was stirred until a clear solution was obtained The reaction was quenched by addition of concentrated hydrochloric acid until pH=3 After stirring for 17 h the mixture the product was extracted into dichloromethane The combined organic phases were washed with water, brine dried over sodium sulfate concentrated under reduced pressure

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

実験手順: To a solution of 4-bromobenzaldehyde (100 g, 0.54 mol) and glycinamide hydrochloride (54 g, 0.48 mol) methanol/water (1500 ml, 5.5/1) was added sodium hydroxide (21.6 g, 0.54 mol). After stirring for 17 h at room temperature the reaction mixture was cooled to 0° C. Sodium borohydride (38 g, 1.0 mol) was added and the mixture was stirred until a clear solution was obtained. The reaction was quenched by addition of concentrated hydrochloric acid until pH=3. After stirring for 17 h the mixture was neutralized with a saturated aqueous solution of sodium hydrogen carbonate and the product was extracted into dichloromethane. The combined organic phases were washed with water, brine, dried over sodium sulfate and concentrated under reduced pressure to afford 2-(4-bromobenzylamino)acetamide (92 g). was cooled to 0° C the mixture was stirred until a clear solution was obtained The reaction was quenched by addition of concentrated hydrochloric acid until pH=3 After stirring for 17 h the mixture the product was extracted into dichloromethane The combined organic phases were washed with water, brine dried over sodium sulfate concentrated under reduced pressure

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

実験手順: A mixture of 2-(4-bromobenzylamino)acetamide (1B3) (45.9 mmol, 11.2 g) and carbonyldiimidazole (68.8 mmol, 11.2 g) in acetonitrile (223 ml) was cooled to 0° C. with stirring and 4-dimethylaminopyridine (45.9 mmol, 5.60 g) was added. The mixture was stirred at 0° C. for 24 h and then heated at 80° C. for 18 h. The reaction mixture was diluted with water and the acetonitrile removed under reduced pressure. The mixture was acidified to pH 4 with aqueous HCl and the precipitate collected by filtration and dried in a vacuum oven to give 1-(4-bromobenzyl)imidazolidine-2,4-dione (1B4) 2.55 g (20.2%); 1H NMR (400 MHz, DMSOd6) δ 10.94 (bs, NH) 7.55 (d, 2H) 7.24 (d, 2H) 4.42 (s, 2H) 3.86 (s, 2H). The mixture was stirred at 0° C. for 24 h heated at 80° C. for 18 h the acetonitrile removed under reduced pressure the precipitate collected by filtration dried in a vacuum oven

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To glycinamide hydrochloride (1B2) (129 mmol, 15.4 g) in methanol (343 ml) was added potassium hydroxide (9.27 mmol, 0.520 g) followed by 4-bromobenzaldehyde (1B1) (93 mmol, 17.15 g) and the mixture stirred for 15 minutes at 0° C. Sodium triacetoxyborohydride (278 mmol, 58.9 g) was added and stirring continued for 1 h. The reaction was diluted with water (75 ml), DCM (300 ml) and saturated sodium chloride solution (100 ml) and the phases separated. The aqueous layer was washed twice with DCM (100 ml) before addition of sodium hydroxide solution to ˜pH10 and the resulting precipitate was collected by filtration to give 2-(4-bromobenzylamino)acetamide (1B3) 13.2 g (58.5%); 1H NMR (400 MHz, DMSOd6) δ 7.50 (d, 2H) 7.31 (d, 2H) 7.08 (bs, NH2) 3.65 (s, 2H) 3.01 (s, 2H) 2.58 (bs, NH). stirring continued for 1 h the phases separated The aqueous layer was washed twice with DCM (100 ml) before addition of sodium hydroxide solution to ˜pH10 the resulting precipitate was collected by filtration

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

実験手順: To a solution of 4-bromobenzaldehyde (100 g, 0.54 mol) and glycinamide hydrochloride (54 g, 0.48 mol) methanol/water (1500 ml, 5.5/1) was added sodium hydroxide (21.6 g, 0.54 mol). After stirring for 17 h at room temperature the reaction mixture was cooled to 0° C. Sodium borohydride (38 g, 1.0 mol) was added and the mixture was stirred until a clear solution was obtained. The reaction was quenched by addition of concentrated hydrochloric acid until pH=3. After stirring for 17 h the mixture was neutralized with a saturated aqueous solution of sodium hydrogen carbonate and the product was extracted into dichloromethane. The combined organic phases were washed with water, brine, dried over sodium sulfate and concentrated under reduced pressure to afford 2-(4-bromobenzylamino)acetamide (92 g). was cooled to 0° C the mixture was stirred until a clear solution was obtained The reaction was quenched by addition of concentrated hydrochloric acid until pH=3 After stirring for 17 h the mixture the product was extracted into dichloromethane The combined organic phases were washed with water, brine dried over sodium sulfate concentrated under reduced pressure