tert-butyl 2-(benzylamino)acetate

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

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

Procedure: To a suspension containing 3.00 g (27.0 mmol) of pyrrole-2-carboxylic acid in 75 mL of anhydrous dichloromethane under a nitrogen atmosphere at 0° C. was added 6.96 g (27.0 mmol of BOPCl and 14.1 mL (81.0 mmol) of DIEA. After stirring for 30 minutes, 5.97 g (27.0 mmol) of N-(benzyl)glycine-t-butyl ester was added and the reaction allowed to warm to room temperature overnight. The reaction was diluted with ethyl acetate and washed with a 5% potassium hydrogensulfate, saturated sodium bicarbonate solution and brine. The organic phase was dried over magnesium sulfate, filtered and evaporated under reduced pressure. The residue was purified by column chromatography on silica gel using a gradient of 100% hexane to 60% hexane/ethyl acetate to afford 2.92 g (34.4%) of the title compound is a white solid. FAB MS [M+H] m/z Calcd: 315, Found: 315. washed with a 5% potassium hydrogensulfate, saturated sodium bicarbonate solution and brine The organic phase was dried over magnesium sulfate filtered evaporated under reduced pressure The residue was purified by column chromatography on silica gel using a gradient of 100% hexane to 60% hexane/ethyl acetate

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

Procedure: To 71.0 g of benzylamine in 100 ml of benzene was added with stirring 25.0 g of tert-butyl chloroacetate over a period of 30 minutes, while maintaining the temperature at 30°-70° C. The reaction mixture was held at 70° C for an additional 1 hour. At the end of this period, the reaction mixture was taken up in 70 ml of 2N NaOH solution and 80 ml of benzene, transferred into a separatory funnel and well shaken. The benzene solution was separated, washed with water, dried over anhydrous sodium sulfate and filtered. After evaporation of benzene, the residue was distilled under reduced pressure to give 32.7 g (89.0 percent) of N-benzylglycine tert-butyl ester, B.P. 120°-125° C/ 2 mmHg. while maintaining the temperature at 30°-70° C The benzene solution was separated washed with water dried over anhydrous sodium sulfate filtered After evaporation of benzene the residue was distilled under reduced pressure

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

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

Conditions: temp:2.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 40 g (205 mmol, 1 eq.) tert-butyl bromoacetate were dissolved in 200 ml CH3CN. The solution was cooled to 0-5° C. and 47 g benzylamine (2.14 eq.) in solution in 90 ml CH3CN were added over 15 min. After 5 min, the reaction mixture was warmed to RT and stirred for 3 h (IPC by GC). The resulting suspension was filtered and evaporated to constant weight to give 49 g of a yellow oil. The oil was dissolved in 200 ml heptane and washed 3 times with 50 ml aq. NaHCO3 solution. The organic phase was dried over sodium sulfate, filtered and evaporated to give 35.8 g of the crude product. Distillation under high vacuum afforded 27.2 g of the title product (95% pure by GC). the reaction mixture was warmed to RT The resulting suspension was filtered evaporated to constant weight

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

Procedure: 10.5 g (54.7 mmol, 1 eq.) 1-(2-oxo-ethyl)-cyclopropanecarboxylic acid tert-butyl ester and 13.21 g (1.08 eq.) N-benzylglycine tert-butyl ester were dissolved in 140 ml toluene. 21 g (1.63 eq.) sodium triacetoxyborohydride were added (exotherm from 25° C. to 28° C.) and the reaction mixture was stirred 5 h at RT (IPC by GC). A solution of 2 ml (0.64 eq.) AcOH in 15 ml toluene was added. After 30 min at RT, the reaction mixture was cooled to 0° C. and 100 ml sat. aq. NaHCO3 solution was added over 40 min (foaming). 50 ml EtOAc were added. The mixture was stirred for 30 min at RT. The mixture was extracted with 200 ml and a second time with 50 ml EtOAc. The organic phases were washed with 50 ml sat. aq. NaHCO3 solution followed by 50 ml sat. aq. NaCl solution. The organic phases were combined, dried over sodium sulfate, filtered and concentrated under reduced pressure to give 21.5 g of the title compound as an oil (ca. 95% yield, corrected for ca 3% residual toluene and 3% amine starting material). After 30 min at RT the reaction mixture was cooled to 0° C. The mixture was stirred for 30 min at RT The mixture was extracted with 200 ml The organic phases were washed with 50 ml sat. aq. NaHCO3 solution dried over sodium sulfate filtered concentrated under reduced pressure

Conditions: temp:2.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 40 g (205 mmol, 1 eq.) tert-butyl bromoacetate were dissolved in 200 ml acetonitrile. The solution was cooled to 0-5° C. and 47 g benzylamine (2.14 eq.) in solution in 90 ml acetonitrile were added over 15 min. After 5 min, the reaction mixture was warmed to room temperature and stirred for 3 h (IPC by GC). The resulting suspension was filtered and evaporated to constant weight to give 49 g of a yellow oil. The oil was dissolved in 200 ml heptane and washed 3 times with 50 ml aq. sodium hydrogencarbonate solution. The organic phase was dried over sodium sulfate, filtered and evaporated to give 35.8 g of the crude product. Distillation under high vacuum afforded 27.2 g of the title product (95% pure by GC). the reaction mixture was warmed to room temperature The resulting suspension was filtered evaporated to constant weight

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

Procedure: 10.5 g (54.7 mmol, 1 eq.) 1-(2-oxo-ethyl)-cyclopropanecarboxylic acid tert-butyl ester and 13.21 g (1.08 eq.) N-benzylglycine tert-butyl ester were dissolved in 140 ml toluene. 21 g (1.63 eq.) sodium triacetoxyborohydride were added (exotherm from 25° C. to 28° C.) and the reaction mixture was stirred 5 h at room temperature (IPC by GC). A solution of 2 ml (0.64 eq.) acetic acid in 15 ml toluene was added. After 30 min at room temperature, the reaction mixture was cooled to 0° C. and 100 ml sat. aq. sodium hydrogencarbonate solution was added over 40 min (foaming). 50 ml ethyl acetate were added. The mixture was stirred for 30 min at room temperature. The mixture was extracted with 200 ml and a second time with 50 ml ethyl acetate. The organic phases were washed with 50 ml sat. aq. sodium hydrogencarbonate solution followed by 50 ml sat. aq. sodium chloride solution. The organic phases were combined, dried over sodium sulfate, filtered and concentrated under reduced pressure to give 21.5 g of the title compound as an oil (ca. 95% yield, corrected for ca 3% residual toluene and 3% amine starting material). After 30 min at room temperature the reaction mixture was cooled to 0° C. The mixture was stirred for 30 min at room temperature The mixture was extracted with 200 ml The organic phases were washed with 50 ml sat. aq. sodium hydrogencarbonate solution dried over sodium sulfate filtered concentrated under reduced pressure

Conditions: temp:2.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 40 g (205 mmol, 1 equiv.) tert-butyl bromoacetate were dissolved in 200 ml acetonitrile. The solution was cooled to 0-5° C. and 47 g benzylamine (2.14 equiv.) in solution in 90 ml acetonitrile were added over 15 min. After 5 min, the reaction mixture was warmed to room temperature and stirred for 3 h (IPC by GC). The resulting suspension was filtered and evaporated to constant weight to give 49 g of a yellow oil. The oil was dissolved in 200 ml heptane and washed 3 times with 50 ml aq. sodium hydrogencarbonate solution. The organic phase was dried over sodium sulfate, filtered and evaporated to give 35.8 g of the crude product. Distillation under high vacuum afforded 27.2 g of the title product (95% pure by GC). the reaction mixture was warmed to room temperature The resulting suspension was filtered evaporated to constant weight

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

Procedure: 10.5 g (54.7 mmol, 1 equiv.) 1-(2-oxo-ethyl)-cyclopropanecarboxylic acid tert-butyl ester and 13.21 g (1.08 equiv.) N-benzylglycine tert-butyl ester were dissolved in 140 ml toluene. 21 g (1.63 equiv.) sodium triacetoxyborohydride were added (exotherm from 25° C. to 28° C.) and the reaction mixture was stirred 5 h at room temperature (IPC by GC). A solution of 2 ml (0.64 equiv.) acetic acid in 15 ml toluene was added. After 30 min at room temperature, the reaction mixture was cooled to 0° C. and 100 ml sat. aq. sodium hydrogencarbonate solution was added over 40 min (foaming). 50 ml ethyl acetate were added. The mixture was stirred for 30 min at room temperature. The mixture was extracted with 200 ml and a second time with 50 ml ethyl acetate. The organic phases were washed with 50 ml sat. aq. sodium hydrogencarbonate solution followed by 50 ml sat. aq. sodium chloride solution. The organic phases were combined, dried over sodium sulfate, filtered and concentrated under reduced pressure to give 21.5 g of the title compound as an oil (ca. 95% yield, corrected for ca 3% residual toluene and 3% amine starting material). After 30 min at room temperature the reaction mixture was cooled to 0° C. The mixture was stirred for 30 min at room temperature The mixture was extracted with 200 ml The organic phases were washed with 50 ml sat. aq. sodium hydrogencarbonate solution dried over sodium sulfate filtered concentrated under reduced pressure

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

Procedure: To a suspension containing 3.00 g (27.0 mmol) of pyrrole-2-carboxylic acid in 75 mL of anhydrous dichloromethane under a nitrogen atmosphere at 0° C. was added 6.96 g (27.0 mmol of BOPCl and 14.1 mL (81.0 mmol) of DIEA. After stirring for 30 minutes, 5.97 g (27.0 mmol) of N-(benzyl)glycine-t-butyl ester was added and the reaction allowed to warm to room temperature overnight. The reaction was diluted with ethyl acetate and washed with a 5% potassium hydrogensulfate, saturated sodium bicarbonate solution and brine. The organic phase was dried over magnesium sulfate, filtered and evaporated under reduced pressure. The residue was purified by column chromatography on silica gel using a gradient of 100% hexane to 60% hexane/ethyl acetate to afford 2.92 g (34.4%) of the title compound is a white solid. FAB MS [M+H] m/z Calcd: 315, Found: 315. washed with a 5% potassium hydrogensulfate, saturated sodium bicarbonate solution and brine The organic phase was dried over magnesium sulfate filtered evaporated under reduced pressure The residue was purified by column chromatography on silica gel using a gradient of 100% hexane to 60% hexane/ethyl acetate