tert-butyl N-[2-[methoxy(methyl)amino]-2-oxoethyl]carbamate

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: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 tert-butyl 2-(methoxy(methyl)amino)-2-oxoethylcarbamate (400 mg, 1.83 mmol) in THF (10 mL) was added cyclohexylmagnesium chloride (4.12 mL, 8.24 mmol) portionwise at room temperature under N2 atmosphere. As addition of the Grignard reagent was completed, the reaction mixture was stirred and heated to reflux for an hour. Then the mixture was allowed to cool down to room temperature. The reaction was quenched by adding water (10 mL) slowly. 1N HCl solution (30 mL) was added to the mixture, and extracted with EtOAc (20 mL×3). The combined organic layers were collected and evaporated in vacuo. The crude material was purified by column chromatography (hexane: EtOAc=10:1 to 5:1) to yield the desired product (110 mg, 25%). heated to reflux for an hour The reaction was quenched by adding water (10 mL) slowly 1N HCl solution (30 mL) was added to the mixture extracted with EtOAc (20 mL×3) The combined organic layers were collected evaporated in vacuo The crude material was purified by column chromatography (hexane: EtOAc=10:1 to 5:1)

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

実験手順: To a tert-butyl 2-(methoxy(methyl)amino)-2-oxoethylcarbamate (400 mg, 1.83 mmol) in THF (10 mL) was added cyclohexylmagnesium chloride (4.12 mL, 8.24 mmol) portionwise at room temperature under N2 atmosphere. As addition of the Grignard reagent was completed, the reaction mixture was stirred and heated to reflux for an hour. Then the mixture was allowed to cool down to room temperature. The reaction was quenched by adding water (10 mL) slowly. 1N HCl solution (30 mL) was added to the mixture, and extracted with EtOAc (20 mL×3). The combined organic layers were collected and evaporated in vacuo. The crude material was purified by column chromatography (hexane: EtOAc=10:1 to 5:1) to yield the desired product (110 mg, 25%). heated to reflux for an hour The reaction was quenched by adding water (10 mL) slowly 1N HCl solution (30 mL) was added to the mixture extracted with EtOAc (20 mL×3) The combined organic layers were collected evaporated in vacuo The crude material was purified by column chromatography (hexane: EtOAc=10:1 to 5:1)

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

実験手順: To a 2-(tert-butoxycarbonylamino)acetic acid (800 mg, 4.57 mmol), N,O-dimethylhydroxylamine hydrochloride (535 mg, 5.48 mmol), EDCI (1.05 g, 5.48 mmol), HOBt (740 mg, 5.48 mmol) in DCM (25 mL) was added NMM (2.77 g, 27.42 mmol) at rt. The reaction mixture was stirred overnight. After the reaction was completed, DCM was evaporated in vacuo. The residue was dissolved in MeOH, filtered through a syringe filter, and then purified by reverse-phase prep HPLC to provide the desired product (705 mg, 71%) as white solid DCM was evaporated in vacuo The residue was dissolved in MeOH filtered through a syringe filter purified by reverse-phase prep HPLC

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

実験手順: To a 2-(tert-butoxycarbonylamino)acetic acid (800 mg, 4.57 mmol), N,O-dimethylhydroxylamine hydrochloride (535 mg, 5.48 mmol), EDCI (1.05 g, 5.48 mmol), HOBt (740 mg, 5.48 mmol) in DCM (25 mL) was added NMM (2.77 g, 27.42 mmol) at rt. The reaction mixture was stirred overnight. After the reaction was completed, DCM was evaporated in vacuo. The residue was dissolved in MeOH, filtered through a syringe filter, and then purified by reverse-phase prep HPLC to provide the desired product (705 mg, 71%) as white solid DCM was evaporated in vacuo The residue was dissolved in MeOH filtered through a syringe filter purified by reverse-phase prep HPLC

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

実験手順: 8.75 g (50 mmol) of BOC-glycine dissolved in 150 ml DCM and 6,95 ml (50 mmol) of TEA was added to the solution, and stirred. 17.42 g (50 mmol) BOP reagent (Richelieu Biotechnologies, QC, Canada) was added, followed a few minutes later with O,N-dimethyl-hydroxylamine hydrochloride (5.6 g, 55 mmol) and TEA (7.67 g, 55 mmol). The reaction was complete in 60 min, and the result was verified by TLC monitoring. A small amount of TEA was used to neutralize the mixture (adjust the pH to above 7.0) in order to allow the reaction to go to completion. The mixture was diluted to 500 ml with DCM. The solution was washed in turn with 3N HCl (3×100 ml), saturated NaHCO3 (3×100 ml), and brine (3×100 ml). The DCM layer was dried over MgSO4 and concentrated to obtain the crude product. Recrystallization from water afforded 5.85 g Nα -(BOC)-glycine N-methoxy-N-methylamide (m.p. 92°-95° C.). This product was dried thoroughly in vacuo over P2O5 before use in the following reaction. the reaction The solution was washed in turn with 3N HCl (3×100 ml), saturated NaHCO3 (3×100 ml), and brine (3×100 ml) The DCM layer was dried over MgSO4 concentrated to obtain the crude product Recrystallization from water