tert-butyl N-[4-[methoxy(methyl)amino]-4-oxobutyl]carbamate

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of 11-3 (10.0 g, 40.5 mmol) and THF (200 ml) at 0° C. was added methylmagnesium bromide (27.0 ml, 91.0 mmol; 3M in ether) dropwise over 20 minutes. After 2.0 hours, 10% KHSO4 was added slowly. The mixture was extracted with EtOAc. The organic portion was washed with sat. NaHCO3, brine, and dried over MgSO4. Evaporative removal of the solvent gave 11-4 as a colorless oil. The mixture was extracted with EtOAc The organic portion was washed with sat. NaHCO3, brine dried over MgSO4 Evaporative removal of the solvent

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of 11-3 (10.0 g, 40.5 mmol) and THF (200 ml) at 0° C. was added methylmagnesium bromide (27.0 ml, 91.0 mmol; 3M in ether) dropwise over 20 minutes. After 2.0 hours, 10% KHSO4 was added slowly. The mixture was extracted with EtOAc. The organic portion was washed with sat. NaHCO3, brine, and dried over MgSO4. Evaporative removal of the solvent gave 11-4 as a colorless oil. The mixture was extracted with EtOAc The organic portion was washed with sat. NaHCO3, brine dried over MgSO4 Evaporative removal of the solvent

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of 11-3 (10.0 g, 40.5 mmol) and THF (200 ml) at 0° C. was added methylmagnesium bromide (27.0 ml, 91.0 mmol; 3M in ether) dropwise over 20 minutes. After 2.0 hours, 10% KHSO4 was added slowly. The mixture was extracted with EtOAc. The organic portion was washed with sat. NaHCO3, brine, and dried over MgSO4. Evaporative removal of the solvent gave 11-4 as a colorless oil. The mixture was extracted with EtOAc The organic portion was washed with sat. NaHCO3, brine dried over MgSO4 Evaporative removal of the solvent

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: While under an atmosphere of nitrogen, a flame-dried round-bottomed flask was charged with magnesium (3.95 g, 0.162 mol) a small crystal of I2 and just enough dry THF to cover the magnesium. The mixture was heated to reflux until the color dissipated (about 10 min.). Next, a solution of 4-bromo-1-butene (16.4 mL, 0.162 mmol) in dry THF (70 mL) was added and heating was continued for 10 min. After cooling to room temperature, the newly formed Grignard reagent was then added to a ice-cooled solution of tert-butyl 4-(methoxy(methyl)amino)-4-oxobutylcarbamate (10 g, 0.041 mol) in dry THF (100 mL). After stirring overnight at room temperature, the solution was poured into saturated aqueous ammonium chloride (70 mL) and extracted with ether (2×). The organic extracts were combined and washed successively with 1.0 M aq HCl and sat'd aq sodium chloride, dried over MgSO4, filtered and concentrated. Purification by flash column chromatography (15-30% ethyl acetate in hexanes) gave tert-butyl 4-oxooct-7-enylcarbamate as a colorless oil (6.04 g, 62%). ESI MS found for C13H23NO3 m/z [264.3 (M+Na+)]. The mixture was heated to reflux until the color (about 10 min.) heating extracted with ether (2×) washed successively with 1.0 M aq HCl dried over MgSO4 filtered concentrated Purification by flash column chromatography (15-30% ethyl acetate in hexanes)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: While under an atmosphere of argon, a room temperature solution of 4-(tert-butoxycarbonylamino) butanoic acid (20 g, 0.098 mol) in dichloromethane (280 mL, 0.35 M) was treated with CDI (17.6 g, 0.108 mol). After 1.5 hr, O,N-dimethylhydroxylamine hydrochloride (10.6 g; 0.108 mol) was added, and the resulting solution was stirred overnight. The mixture was added to a separatory funnel, diluted with dichloromethane (220 mL) and washed successively with 2 M HCl (2×), 1 M NaOH and sat'd aq sodium chloride, dried over MgSO4, filtered and concentrated to give tert-butyl 4-(methoxy(methyl)amino)-4-oxobutylcarbamate (23.8 g, 98%). ESI MS found for C11H22N2O4 m/z [269.4 (M+Na+)]. The mixture was added to a separatory funnel washed successively with 2 M HCl (2×), 1 M NaOH dried over MgSO4 filtered concentrated

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of 11-3 (10.0 g, 40.5 mmol) and THF (200 ml) at 0° C. was added methylmagnesium bromide (27.0 ml, 91.0 mmol; 3M in ether) dropwise over 20 minutes. After 2.0 hours, 10% KHSO4 was added slowly. The mixture was extracted with EtOAc. The organic portion was washed with sat. NaHCO3, brine, and dried over MgSO4. Evaporative removal of the solvent gave 11-4 as a colorless oil. The mixture was extracted with EtOAc The organic portion was washed with sat. NaHCO3, brine dried over MgSO4 Evaporative removal of the solvent

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of 1-3 (10.0 g, 40.5 mmol) and THF (200 ml) at 0° C. was added methyl magnesium bromide (27.0 ml, 91.0 mmol; 3M in ether) dropwise over 20 minutes. Mter 2.0 hours, 10% KHSO4 was added slowly. The mixture was extracted with EtOAc. The organic portion was washed with saturated NaHCO3, brine, and dried over MgSO4. Evaporative removal of the solvent gave 1-4 as a colorless oil. The mixture was extracted with EtOAc The organic portion was washed with saturated NaHCO3, brine dried over MgSO4 Evaporative removal of the solvent

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of 1-3 (10.0 g, 40.5 mmol) and THF (200 ml) at 0° C. was added methyl magnesium bromide (27.0 ml, 91.0 mmol; 3M in ether) dropwise over 20 minutes. Mter 2.0 hours, 10% KHSO4 was added slowly. The mixture was extracted with EtOAc. The organic portion was washed with saturated NaHCO3, brine, and dried over MgSO4. Evaporative removal of the solvent gave 1-4 as a colorless oil. The mixture was extracted with EtOAc The organic portion was washed with saturated NaHCO3, brine dried over MgSO4 Evaporative removal of the solvent

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of 11-3 (10.0 g, 40.5 mmol) and THF (200 ml) at 0° C. was added methylmagnesium bromide (27.0 ml, 91.0 mmol; 3M in ether) dropwise over 20 minutes. After 2.0 hours, 10% KHSO4 was added slowly. The mixture was extracted with EtOAc. The organic portion was washed with sat. NaHCO3, brine, and dried over MgSO4. Evaporative removal of the solvent gave 11-4 as a colorless oil. The mixture was extracted with EtOAc The organic portion was washed with sat. NaHCO3, brine dried over MgSO4 Evaporative removal of the solvent

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of 11-3 (10.0 g, 40.5 mmol) and THF (200 ml) at 0° C. was added methylmagnesium bromide (27.0 ml, 91.0 mmol; 3M in ether) dropwise over 20 minutes. After 2.0 hours, 10% KHSO4 was added slowly. The mixture was extracted with EtOAc. The organic portion was washed with sat. NaHCO3, brine, and dried over MgSO4. Evaporative removal of the solvent gave 11-4 as a colorless oil. The mixture was extracted with EtOAc The organic portion was washed with sat. NaHCO3, brine dried over MgSO4 Evaporative removal of the solvent