benzyl N-[1-[methoxy(methyl)amino]-2-methyl-1-oxopropan-2-yl]carbamate

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

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

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Diisobutylaluminum hydride (1.77 mL, 1M solution in toluene, 0.708 mmol) was added to a stirred solution of benzyl {2-[methoxy(methyl)amino]-1,1-dimethyl-2-oxoethyl}carbamate (198.5 mg, 0.708 mmol) in dry THF (7.1 mL) at −78° C. under N2. The reaction was stirred at −78° C. for 4 h. MeOH (100 mL) and 1N HCl (250 μL) were added and the reaction was allowed to warm to room temperature. The mixture was diluted with Et2O (50 mL) and washed with 1N HCl (2×50 mL), 50% saturated NaHCO3 (50 mL) and water (50 mL), then dried (MgSO4) and concentrated in vacuo to give benzyl (1,1-dimethyl-2-oxoethyl)carbamate. Rf=0.40 (20% EtOAc in hexanes). LCMS calc.=244.1; found=244.1 (M+Na)+. 1H NMR (500 MHz, CDCl3) δ 9.43 (s, 1H), 7.38-7.30 (m, 5H), 5.34 (s, 1H), 5.09 (s, 2H), 1.37 (s, 6H). to warm to room temperature washed with 1N HCl (2×50 mL), 50% saturated NaHCO3 (50 mL) and water (50 mL) dried (MgSO4) concentrated in vacuo

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

Procedure: N-Methylmorpholine (682 mg, 741 μL, 6.74 mmol) and isobutylchloroformate (460 mg, 441 μL, 3.37 mmol) were added successively to a stirred solution of N-carbobenzyloxy-2-methylalanine (0.64 g, 2.69 mmol) in dry CH2Cl2 at 0° C. under N2. The resulting cloudy mixture was stirred at 0° C. for 90 min. N,O-Dimethylhydroxylamine hydrochloride (316 mg, 3.24 mmol) was added portionwise and the mixture was warmed to room temperature and stirred for 3 h. The mixture was poured into 1N HCl (30 mL) and extracted with CH2Cl2 (3×40 mL). The combined extracts were washed with 1N HCl (30 mL), dried (Na2SO4) and concentrated in vacuo to give the crude product. This was purified by flash chromatography (Si, 40×160 mm, 0-80% EtOAc in hexanes gradient) to afford benzyl {2-[methoxy(methyl)amino]-1,1-dimethyl-2-oxoethyl}carbamate. Rf=0.47 (50% EtOAc in hexanes). LCMS calc.=303.1; found=303.2 (M±Na)+. 1H NMR (500 MHz, CDCl3) δ 7.37-7.29 (m, 5H), 5.82 (s, 1H), 5.09 (s, 2H), 3.60 (s, 3H), 3.18 (s, 3H), 1.60 (s, 6H). the mixture was warmed to room temperature stirred for 3 h extracted with CH2Cl2 (3×40 mL) The combined extracts were washed with 1N HCl (30 mL) dried (Na2SO4) concentrated in vacuo to give the crude product This was purified by flash chromatography (Si, 40×160 mm, 0-80% EtOAc in hexanes gradient)

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Diisobutylaluminum hydride (1.77 mL, 1M solution in toluene, 0.708 mmol) was added to a stirred solution of benzyl {2-[methoxy(methyl)amino]-1,1-dimethyl-2-oxoethyl}carbamate (198.5 mg, 0.708 mmol) in dry THF (7.1 mL) at −78° C. under N2. The reaction was stirred at −78° C. for 4 h. MeOH (100 μL) and 1N HCl (250 μL) were added and the reaction was allowed to warm to room temperature. The mixture was diluted with Et2O (50 mL) and washed with 1N HCl (2×50 mL), 50% saturated NaHCO3 (50 mL) and water (50 mL), then dried (MgSO4) and concentrated in vacuo to give benzyl (1,1-dimethyl-2-oxoethyl)carbamate. Rf=0.40 (20% EtOAc in hexanes). LCMS calc.=244.1; found=244.1 (M+Na)+. 1H NMR (500 MHz, CDCl3) δ 9.43 (s, 1H), 7.38-7.30 (m, 5H), 5.34 (s, 1H), 5.09 (s, 2H), 1.37 (s, 6H). to warm to room temperature washed with 1N HCl (2×50 mL), 50% saturated NaHCO3 (50 mL) and water (50 mL) dried (MgSO4) concentrated in vacuo

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

Procedure: N-Methylmorpholine (682 mg, 741 μL, 6.74 mmol) and isobutylchloroformate (460 mg, 441 μL, 3.37 mmol) were added successively to a stirred solution of N-carbobenzyloxy-2-methylalanine (0.64 g, 2.69 mmol) in dry CH2Cl2 at 0° C. under N2. The resulting cloudy mixture was stirred at 0° C. for 90 min. N,O-Dimethylhydroxylamine hydrochloride (316 mg, 3.24 mmol) was added portionwise and the mixture was warmed to room temperature and stirred for 3 h. The mixture was poured into 1N HCl (30 mL) and extracted with CH2Cl2 (3×40 mL). The combined extracts were washed with 1N HCl (30 mL), dried (Na2SO4) and concentrated in vacuo to give the crude product. This was purified by flash chromatography (Si, 40×160 mm, 0-80% EtOAc in hexanes gradient) to afford benzyl {2-[methoxy(methyl)amino]-1,1-dimethyl-2-oxoethyl}carbamate. Rf=0.47 (50% EtOAc in hexanes). LCMS calc.=303.1; found=303.2 (M+Na)+. 1H NMR (500 MHz, CDCl3) δ 7.37-7.29 (m, 5H), 5.82 (s, 1H), 5.09 (s, 2H), 3.60 (s, 3H), 3.18 (s, 3H), 1.60 (s, 6H). the mixture was warmed to room temperature stirred for 3 h extracted with CH2Cl2 (3×40 mL) The combined extracts were washed with 1N HCl (30 mL) dried (Na2SO4) concentrated in vacuo to give the crude product This was purified by flash chromatography (Si, 40×160 mm, 0-80% EtOAc in hexanes gradient)

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

Procedure: N-Methylmorpholine (682 mg, 741 μL, 6.74 mmol) and isobutylchloroformate (460 mg, 441 μL, 3.37 mmol) were added successively to a stirred solution of N-carbobenzyloxy-2-methylalanine (0.64 g, 2.69 mmol) in dry CH2Cl2 at 0° C. under N2. The resulting cloudy mixture was stirred at 0° C. for 90 min. N,O-Dimethylhydroxylamine hydrochloride (316 mg, 3.24 mmol) was added portionwise and the mixture was warmed to room temperature and stirred for 3 h. The mixture was poured into 1N HCl (30 mL) and extracted with CH2Cl2 (3×40 mL). The combined extracts were washed with 1N HCl (30 mL), dried (Na2SO4) and concentrated in vacuo to give the crude product. This was purified by flash chromatography (Si, 40×160 mm, 0-80% EtOAc in hexanes gradient) to afford benzyl {2-[methoxy(methyl)amino]-1,1-dimethyl-2-oxoethyl}carbamate. Rf=0.47 (50% EtOAc in hexanes). LCMS calc.=303.1; found=303.2 (M+Na)+. 1H NMR (500 MHz, CDCl3) δ 7.37-7.29 (m, 5H), 5.82 (s, 1H), 5.09 (s, 2H), 3.60 (s, 3H), 3.18 (s, 3H), 1.60 (s, 6H). the mixture was warmed to room temperature stirred for 3 h extracted with CH2Cl2 (3×40 mL) The combined extracts were washed with 1N HCl (30 mL) dried (Na2SO4) concentrated in vacuo to give the crude product This was purified by flash chromatography (Si, 40×160 mm, 0-80% EtOAc in hexanes gradient)

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

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

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Diisobutylaluminum hydride (1.77 mL, 1M solution in toluene, 0.708 mmol) was added to a stirred solution of benzyl {2-[methoxy(methyl)amino]-1,1-dimethyl-2-oxoethyl}carbamate (198.5 mg, 0.708 mmol) in dry THF (7.1 mL) at −78° C. under N2. The reaction was stirred at −78° C. for 4 h. MeOH (100 μt) and 1N HCl (250 μL) were added and the reaction was allowed to warm to room temperature. The mixture was diluted with Et2O (50 mL) and washed with 1N HCl (2×50 mL), 50% saturated NaHCO3 (50 mL) and water (50 mL), then dried (MgSO4) and concentrated in vacuo to give benzyl (1,1-dimethyl-2-oxoethyl)carbamate. Rf=0.40 (20% EtOAc in hexanes). LCMS calc.=244.1; found=244.1 (M+Na)+. 1H NMR (500 MHz, CDCl3) δ 9.43 (s, 1H), 7.38-7.30 (m, 5H), 5.34 (s, 1H), 5.09 (s, 2H), 1.37 (s, 6H). to warm to room temperature washed with 1N HCl (2×50 mL), 50% saturated NaHCO3 (50 mL) and water (50 mL) dried (MgSO4) concentrated in vacuo

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

Procedure: N-Methylmorpholine (682 mg, 741 μL, 6.74 mmol) and isobutylchloroformate (460 mg, 441 μL, 3.37 mmol) were added successively to a stirred solution of N-carbobenzyloxy-2-methylalanine (0.64 g, 2.69 mmol) in dry CH2Cl2 at 0° C. under N2. The resulting cloudy mixture was stirred at 0° C. for 90 min. N,O-Dimethylhydroxylamine hydrochloride (316 mg, 3.24 mmol) was added portionwise and the mixture was warmed to room temperature and stirred for 3 h. The mixture was poured into 1N HCl (30 mL) and extracted with CH2Cl2 (3×40 mL). The combined extracts were washed with 1N HCl (30 mL), dried (Na2SO4) and concentrated in vacuo to give the crude product. This was purified by flash chromatography (Si, 40×160 mm, 0-80% EtOAc in hexanes gradient) to afford benzyl {2-[methoxy(methyl)amino]-1,1-dimethyl-2-oxoethyl}carbamate. Rf=0.47 (50% EtOAc in hexanes). LCMS calc.=303.1; found=303.2 (M+Na)+. 1H NMR (500 MHz, CDCl3) δ 7.37-7.29 (m, 5H), 5.82 (s, 1H), 5.09 (s, 2H), 3.60 (s, 3H), 3.18 (s, 3H), 1.60 (s, 6H). the mixture was warmed to room temperature stirred for 3 h extracted with CH2Cl2 (3×40 mL) The combined extracts were washed with 1N HCl (30 mL) dried (Na2SO4) concentrated in vacuo to give the crude product This was purified by flash chromatography (Si, 40×160 mm, 0-80% EtOAc in hexanes gradient)

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Diisobutylaluminum hydride (1.77 mL, 1M solution in toluene, 0.708 mmol) was added to a stirred solution of benzyl {2-[methoxy(methyl)amino]-1,1-dimethyl-2-oxoethyl}carbamate (198.5 mg, 0.708 mmol) in dry THF (7.1 mL) at −78° C. under N2. The reaction was stirred at −78° C. for 4 h. MeOH (100 μL) and 1N HCl (250 μL) were added and the reaction was allowed to warm to room temperature. The mixture was diluted with Et2O (50 mL) and washed with 1N HCl (2×50 mL), 50% saturated NaHCO3 (50 mL) and water (50 mL), then dried (MgSO4) and concentrated in vacuo to give benzyl (1,1-dimethyl-2-oxoethyl)carbamate. Rf=0.40 (20% EtOAc in hexanes). LCMS calc.=244.1; found=244.1 (M+Na)+. 1H NMR (500 MHz, CDCl3) δ 9.43 (s, 1H), 7.38-7.30 (m, 5H), 5.34 (s, 1H), 5.09 (s, 2H), 1.37 (s, 6H). to warm to room temperature washed with 1N HCl (2×50 mL), 50% saturated NaHCO3 (50 mL) and water (50 mL) dried (MgSO4) concentrated in vacuo