(R)-叔丁基(1-(甲氧基(甲基)氨基)-1-氧代丙-2-基)氨基甲酸酯

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: The title compound was prepared as Methyl (2E)(4S)-4-[(tert-butoxy)carbonylamino]pent-2-enoate with (2R)-2-[(tert-butoxy)carbonylamino]-N-methoxy-N-methylpropanamide (13.05 grams, 56.18 mmol) to give the title compound (10.2 g, 79%): ES-MS (m/z) 230 [M+1]+.

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: The title compound was prepared as (2S)-2-[(tert-butoxy)carbonylamino]-N-methoxy-N-methylpropanamide with boc-D-alanine (20 grams, 105.7 mmol) to give the title compound (21.7 g, 88%): ES-MS (m/z) 233.2 [M+l]+.

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: In a round-bottomed flask, [(R)-1-(methoxy-methyl-carbamoyl)-ethyl]-carbamic acid tert-butyl ester (300 mg, 1.29 mmol) was dissolved in THF (8 ml). The solution was cooled to −16° C. (NaCl/ice bath) and benzylmagnesium chloride (1.0 M in diethyl ether, 3.8 ml, 3.8 mmol) was added dropwise. After the addition, the reaction mixture was allowed to warm slowly to room temperature and stirred for 5.5 h. The reaction mixture was quenched with saturated aqueous NH4Cl and extracted with EtOAc (2×). The combined organic layers were washed with water and brine then dried over sodium sulfate, filtered and concentrated. The residue was chromatographed over silica gel with EtOAc/hexanes (gradient 0-20% EtOAc) to afford 353 mg (99%) of ((R)-1-methyl-2-oxo-3-phenyl-propyl)-carbamic acid tert-butyl ester as a colorless oil. was added dropwise After the addition The reaction mixture was quenched with saturated aqueous NH4Cl extracted with EtOAc (2×) The combined organic layers were washed with water and brine then dried over sodium sulfate filtered concentrated The residue was chromatographed over silica gel with EtOAc/hexanes (gradient 0-20% EtOAc)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: In a round-bottomed flask, [(R)-1-(methoxy-methyl-carbamoyl)-ethyl]-carbamic acid tert-butyl ester (300 mg, 1.29 mmol) was dissolved in THF (8 ml). The solution was cooled to −16° C. (NaCl/ice bath) and benzylmagnesium chloride (1.0 M in diethyl ether, 3.8 ml, 3.8 mmol) was added dropwise. After the addition, the reaction mixture was allowed to warm slowly to room temperature and stirred for 5.5 h. The reaction mixture was quenched with saturated aqueous NH4Cl and extracted with EtOAc (2×). The combined organic layers were washed with water and brine then dried over sodium sulfate, filtered and concentrated. The residue was chromatographed over silica gel with EtOAc/hexanes (gradient 0-20% EtOAc) to afford 353 mg (99%) of ((R)-1-methyl-2-oxo-3-phenyl-propyl)-carbamic acid tert-butyl ester as a colorless oil. was added dropwise After the addition The reaction mixture was quenched with saturated aqueous NH4Cl extracted with EtOAc (2×) The combined organic layers were washed with water and brine then dried over sodium sulfate filtered concentrated The residue was chromatographed over silica gel with EtOAc/hexanes (gradient 0-20% EtOAc)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: In a round-bottomed flask, [(R)-1-(methoxy-methyl-carbamoyl)-ethyl]-carbamic acid tert-butyl ester (3.00 g, 12.9 mmol) was dissolved in THF (100 ml). The solution was cooled to −16° C. (NaCl/ice bath) and methylmagnesium bromide (3.0 M in diethyl ether, 12.0 ml, 36.0 mmol) was added dropwise over 20 min. After the addition, the reaction mixture was allowed to warm slowly to room temperature overnight. The reaction mixture was cooled to 0° C., quenched with saturated aqueous NH4Cl and extracted with EtOAc (2×). The combined organic layers were washed with water and brine then dried over sodium sulfate, filtered and concentrated. The residue was chromatographed over silica gel with EtOAc/hexanes (gradient 0-20% EtOAc) to afford 2.21 g (91%) of ((R)-1-methyl-2-oxo-propyl)-carbamic acid tert-butyl ester as a white solid. was added dropwise over 20 min After the addition The reaction mixture was cooled to 0° C. quenched with saturated aqueous NH4Cl extracted with EtOAc (2×) The combined organic layers were washed with water and brine then dried over sodium sulfate filtered concentrated The residue was chromatographed over silica gel with EtOAc/hexanes (gradient 0-20% EtOAc)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: In a round-bottomed flask, [(R)-1-(methoxy-methyl-carbamoyl)-ethyl]-carbamic acid tert-butyl ester (3.00 g, 12.9 mmol) was dissolved in THF (100 ml). The solution was cooled to −16° C. (NaCl/ice bath) and methylmagnesium bromide (3.0 M in diethyl ether, 12.0 ml, 36.0 mmol) was added dropwise over 20 min. After the addition, the reaction mixture was allowed to warm slowly to room temperature overnight. The reaction mixture was cooled to 0° C., quenched with saturated aqueous NH4Cl and extracted with EtOAc (2×). The combined organic layers were washed with water and brine then dried over sodium sulfate, filtered and concentrated. The residue was chromatographed over silica gel with EtOAc/hexanes (gradient 0-20% EtOAc) to afford 2.21 g (91%) of ((R)-1-methyl-2-oxo-propyl)-carbamic acid tert-butyl ester as a white solid. was added dropwise over 20 min After the addition The reaction mixture was cooled to 0° C. quenched with saturated aqueous NH4Cl extracted with EtOAc (2×) The combined organic layers were washed with water and brine then dried over sodium sulfate filtered concentrated The residue was chromatographed over silica gel with EtOAc/hexanes (gradient 0-20% EtOAc)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: With the exception that (S)-t-butyl(1-(methoxy(methyl)amino)-1-oxopropan-2-yl)carbamate and 1-bromo-2,6-difluorobenzene were used instead of (R)-t-butyl(1-(methoxy(methyl)amino)-1-oxopropan-2-yl)carbamate and 4-methoxybromobenzene, respectively, the same procedure as in Preparation Example 5-5 was repeated to afford the title compound. 0.26 g (17%). respectively, the same procedure as in Preparation Example 5-5

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: With the exception that (S)-t-butyl(1-(methoxy(methyl)amino)-1-oxopropan-2-yl)carbamate and 1-bromo-2,6-difluorobenzene were used instead of (R)-t-butyl(1-(methoxy(methyl)amino)-1-oxopropan-2-yl)carbamate and 4-methoxybromobenzene, respectively, the same procedure as in Preparation Example 5-5 was repeated to afford the title compound. 0.26 g (17%). respectively, the same procedure as in Preparation Example 5-5

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: With the exception that (S)-t-butyl(1-(methoxy(methyl)amino)-1-oxopropan-2-yl)carbamate and 1-bromo-3,5-difluorobenzene were used instead of (R)-t-butyl(1-(methoxy(methyl)amino)-1-oxopropan-2-yl)carbamate and 4-methoxybromobenzene, respectively, the same procedure as in Preparation Example 5-5 was repeated to afford the title compound. 1.3 g (46%). respectively, the same procedure as in Preparation Example 5-5

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of (R)-t-butyl(1-(methoxy(methyl)amino)-1-oxopropan-2-yl)carbamate (5.0 g, 21.5 mmol) in 50 mL of tetrahydrofuran was cooled to −20° C. 4-Methoxyphenylmagnesium bromide was prepared by stirring magnesium (2.1 g, 86.1 mmol), 4-methoxybromobenzene (16.1 g, 86.1 mmol), and a catalytically effective amount of iodide in 100 mL of tetrahydrofuran, and dropwise added to the solution. A reaction was conducted at 20˜25° C. for 16 hrs while stirring.

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of (R)-t-butyl(1-(methoxy(methyl)amino)-1-oxopropan-2-yl)carbamate (5.0 g, 21.5 mmol) in 50 mL of tetrahydrofuran was cooled to −20° C. 4-Methoxyphenylmagnesium bromide was prepared by stirring magnesium (2.1 g, 86.1 mmol), 4-methoxybromobenzene (16.1 g, 86.1 mmol), and a catalytically effective amount of iodide in 100 mL of tetrahydrofuran, and dropwise added to the solution. A reaction was conducted at 20˜25° C. for 16 hrs while stirring.

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: The title compound was prepared as Methyl (2E)(4S)-4-[(tert-butoxy)carbonylamino]pent-2-enoate with (2R)-2-[(tert-butoxy)carbonylamino]-N-methoxy-N-methylpropanamide (13.05 grams, 56.18 mmol) to give the title compound (10.2 g, 79%): ES-MS (m/z) 230 [M+1]+.