tert-butyl N-[(2S)-4-diazo-3-oxobutan-2-yl]carbamate

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

Procedure: To a vigorously stirred solution of [(t-butyloxy)carbonyl]-L-alanine (15.14 g, 80 mmol) and N-methylmorpholine (8.80 ml, 80 mmol) in 80 ml of dry tetrahydrofuran at -15° C. under argon was added a solution of isobutyl chloroformate (10.37 ml, 80 mmol) in 10 ml tetrahydrofuran, maintaining the reaction temperature below -12° C. After the addition was complete, the reaction mixture was stirred for 14 minutes and then diluted with 250 ml of anhydrous ether (prechilled to -20° C.) and quickly filtered. Approximately one-fourth of the filtrate was transferred to a separatory funnel (the remainder kept chilled) and added rapidly to a gently stirred, chilled (0° C.) solution of diazomethane (160 mmol, generated from 23.54 g of N-methyl-N'-nitro-N-nitrosoguanidine). Additional chilled portions were transferred to the separatory funnel until the entire solution had been added (over approximately 10 minutes). The resulting solution was stirred for 2 hours, warming gradually to room temperature, then purged with nitrogen for 1 hour, washed with chilled half-saturated sodium bicarbonate (2×100 ml) and water (3×50 ml), dried (sodium sulfate) and evaporated to a yellow semi-crystalline residue. Two recrystallizations from ethyl acetate-petroleum ether yielded yellow plates, 10.29 g, melting point 99°-102° C., plus an additional crop of 1.33 g, melting point 97.5°-101° C. A portion was recrystallized once more giving the analytical sample, melting point 102°-103° C. maintaining the reaction temperature below -12° C After the addition quickly filtered Approximately one-fourth of the filtrate was transferred to a separatory funnel (the remainder kept chilled) and added rapidly to a gently stirred Additional chilled portions had been added (over approximately 10 minutes) The resulting solution was stirred for 2 hours purged with nitrogen for 1 hour washed with chilled half-saturated sodium bicarbonate (2×100 ml) and water (3×50 ml) dried (sodium sulfate) evaporated to a yellow semi-crystalline residue Two recrystallizations from ethyl acetate-petroleum ether yielded yellow plates, 10.29 g, melting point 99°-102° C. A portion was recrystallized once more giving the analytical sample, melting point 102°-103° C.

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

Procedure: To a vigorously stirred solution of N-[(1,1-dimethylethoxy)carbonyl]-L-alanine (15.14 g., 80 mmole) and N-methylmorpholine (8.80 ml., 80 mmole) in dry tetrahydrofuran (80 ml.) at -15° under argon is added a solution of isobutyl chloroformate (10.37 ml., 80 mmole) in tetrahydrofuran (10 ml.) while maintaining the reaction temperature below -12°. After the addition is complete, the reaction mixture is stirred for 14 minutes, diluted with anhydrous ether (250 ml., prechilled to -20°), and quickly filtered. Approximately one-fourth of the filtrate is transferred to a separatory funnel (the remainder is kept chilled) and added rapidly to a gently stirred, chilled (0°) solution of diazomethane (160 mmole). Additional chilled portions are transferred to the separatory funnel until the entire solution has been added (approximately 10 minutes). The resulting solution is stirred for 2 hours, warming gently to room temperature, then purged with nitrogen for 1 hour, washed with chilled half-saturated sodium bicarbonate (2×100 ml.) and water (3×50 ml.), dried (Na2SO4), and evaporated to a yellow semi-crystalline residue. Two recrystallizations from ethyl acetate-petroleum ether yield 10.29 g. of product as yellow plates; m.p. 99°-102° plus an additional crop of 1.33 g.; m.p. 97.5°-101°. A portion is recrystallized once more giving an analytically pure sample of (S)-(3-diazo-1-methyl-2-oxopropyl)carbamic acid, 1,1-dimethylethyl ester; m.p. 102°-103°. while maintaining the reaction temperature below -12° After the addition quickly filtered Approximately one-fourth of the filtrate is transferred to a separatory funnel (the remainder is kept chilled) and added rapidly to a gently stirred Additional chilled portions has been added (approximately 10 minutes) The resulting solution is stirred for 2 hours purged with nitrogen for 1 hour washed with chilled half-saturated sodium bicarbonate (2×100 ml.) and water (3×50 ml.) dried (Na2SO4) evaporated to a yellow semi-crystalline residue Two recrystallizations from ethyl acetate-petroleum ether yield 10.29 g A portion is recrystallized once more

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

Procedure: To a vigorously stirred solution of [(t-butyloxy)carbonyl]-L-alanine (15.14 g, 80 mmol) and N-methylmorpholine (8.80 ml, 80 mmol) in 80 ml of dry tetrahydrofuran at -15° C. under argon was added a solution of isobutyl chloroformate (10.37 ml, 80 mmol) in 10 ml tetrahydrofuran, maintaining the reaction temperature below -12° C. After the addition was complete, the reaction mixture was stirred for 14 minutes and then diluted with 250 ml of anhydrous ether (prechilled to -20° C.) and quickly filtered. Approximately one-fourth of the filtrate was transferred to a separatory funnel (the remainder kept chilled) and added rapidly to a gently stirred, chilled (0° C.) solution of diazomethane (160 mmol, generated from 23.54 g of N-methyl-N'-nitro-N-nitrosoguanidine). Additional chilled portions were transferred to the separatory funnel until the entire solution had been added (over approximately 10 minutes). The resulting solution was stirred for 2 hours, warming gradually to room temperature, then purged with nitrogen for 1 hour, washed with chilled half-saturated sodium bicarbonate (2×100 ml) and water (3×50 ml), dried (sodium sulfate) and evaporated to a yellow semi-crystalline residue. Two recrystallizations from ethyl acetate-petroleum ether yielded yellow plates, 10.29 g, melting point 99°-102° C., plus an additional crop of 1.33 g, melting point 97.5°-101° C. A portion was recrystallized once more giving the analytical sample, melting point 102°-103° C. maintaining the reaction temperature below -12° C After the addition quickly filtered Approximately one-fourth of the filtrate was transferred to a separatory funnel (the remainder kept chilled) and added rapidly to a gently stirred Additional chilled portions had been added (over approximately 10 minutes) The resulting solution was stirred for 2 hours purged with nitrogen for 1 hour washed with chilled half-saturated sodium bicarbonate (2×100 ml) and water (3×50 ml) dried (sodium sulfate) evaporated to a yellow semi-crystalline residue Two recrystallizations from ethyl acetate-petroleum ether yielded yellow plates, 10.29 g, melting point 99°-102° C. A portion was recrystallized once more giving the analytical sample, melting point 102°-103° C.

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

Procedure: To a vigorously stirred solution of [(t-butyloxy)carbonyl]-L-alanine (15.14 g, 80 mmol) and N-methylmorpholine (8.80 ml, 80 mmol) in 80 ml of dry tetrahydrofuran at -15° C. under argon was added a solution of isobutyl chloroformate (10.37 ml, 80 mmol) in 10 ml tetrahydrofuran, maintaining the reaction temperature below -12° C. After the addition was complete, the reaction mixture was stirred for 14 minutes and then diluted with 250 ml of anhydrous ether (prechilled to -20° C.) and quickly filtered. Approximately one-fourth of the filtrate was transferred to a separatory funnel (the remainder kept chilled) and added rapidly to a gently stirred, chilled (0° C.) solution of diazomethane (160 mmol, generated from 23.54 g of N-methyl-N'-nitro-N-nitrosoguanidine). Additional chilled portions were transferred to the separatory funnel until the entire solution had been added (over approximately 10 minutes). The resulting solution was stirred for 2 hours, warming gradually to room temperature, then purged with nitrogen for 1 hour, washed with chilled half-saturated sodium bicarbonate (2×100 ml) and water (3×50 ml), dried (sodium sulfate) and evaporated to a yellow semi-crystalline residue. Two recrystallizations from ethyl acetate-petroleum ether yielded yellow plates, 10.29 g, melting point 99°-102° C., plus an additional crop of 1.33 g, melting point 97.5√-101° C. A portion was recrystallized once more giving the analytical sample, melting point 102°-103° C. maintaining the reaction temperature below -12° C After the addition quickly filtered Approximately one-fourth of the filtrate was transferred to a separatory funnel (the remainder kept chilled) and added rapidly to a gently stirred Additional chilled portions had been added (over approximately 10 minutes) The resulting solution was stirred for 2 hours purged with nitrogen for 1 hour washed with chilled half-saturated sodium bicarbonate (2×100 ml) and water (3×50 ml) dried (sodium sulfate) evaporated to a yellow semi-crystalline residue Two recrystallizations from ethyl acetate-petroleum ether yielded yellow plates, 10.29 g, melting point 99°-102° C. point 97.5√-101° C A portion was recrystallized once more giving the analytical sample, melting point 102°-103° C.

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

Procedure: To a vigorously stirred solution of [(t-butyloxy)carbonyl]-L-alanine (15.14 g, 80 mmol) and N-methylmorpholine (8.80 ml, 80 mmol) in 80 ml of dry tetrahydrofuran at -15° C. under argon was added a solution of isobutyl chloroformate (10.37 ml, 80 mmol) in 10 ml tetrahydrofuran, maintaining the reaction temperature below -12° C. After the addition was complete, the reaction mixture was stirred for 14 minutes and then diluted with 250 ml of anhydrous ether (prechilled to -20° C.) and quickly filtered. Approximately one-fourth of the filtrate was transferred to a separatory funnel (the remainder kept chilled) and added rapidly to a gently stirred, chilled (0° C.) solution of diazomethane (160 mmol, generated from 23.54 g of N-methyl-N'-nitro-N-nitrosoguanidine). Additional chilled portions were transferred to the separatory funnel until the entire solution had been added (over approximately 10 minutes). The resulting solution was stirred for 2 hours, warming gradually to room temperature, then purged with nitrogen for 1 hour, washed with chilled half-saturated sodium bicarbonate (2×100 ml) and water (3×50 ml), dried (sodium sulfate) and evaporated to a yellow semi-crystalline residue. Two recrystallizations from ethyl acetate-petroleum ether yielded yellow plates, 10.29 g, melting point 99°-102° C., plus an additional crop of 1.33 g, melting point 97.5°-101° C. A portion was recrystallized once more giving the analytical sample, melting point 102°-103° C. maintaining the reaction temperature below -12° C After the addition quickly filtered Approximately one-fourth of the filtrate was transferred to a separatory funnel (the remainder kept chilled) and added rapidly to a gently stirred Additional chilled portions had been added (over approximately 10 minutes) The resulting solution was stirred for 2 hours purged with nitrogen for 1 hour washed with chilled half-saturated sodium bicarbonate (2×100 ml) and water (3×50 ml) dried (sodium sulfate) evaporated to a yellow semi-crystalline residue Two recrystallizations from ethyl acetate-petroleum ether yielded yellow plates, 10.29 g, melting point 99°-102° C. A portion was recrystallized once more giving the analytical sample, melting point 102°-103° C.

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

Procedure: To a vigorously stirred solution of [(t-butyloxy)carbonyl]-L-alanine (15.14 g, 80 mmol) and N-methylmorpholine (8.80 ml, 80 mmol) in 80 ml of dry tetrahydrofuran at -15° C. under argon was added a solution of isobutyl chloroformate (10.37 ml, 80 mmol) in 10 ml tetrahydrofuran, maintaining the reaction temperature below -12° C. After the addition was complete, the reaction mixture was stirred for 14 minutes and then diluted with 250 ml of anhydrous ether (prechilled to -20° C.) and quickly filtered. Approximately one-fourth of the filtrate was transferred to a separatory funnel (the remainder kept chilled) and added rapidly to a gently stirred, chilled (0° C.) solution of diazomethane (160 mmol, generated from 23.54 g of N-methyl-N'-nitro-N-nitrosoguanidine). Additional chilled portions were transferred to the separatory funnel until the entire solution had been added (over approximately 10 minutes). The resulting solution was stirred for 2 hours, warming gradually to room temperature, then purged with nitrogen for 1 hour, washed with chilled half-saturated sodium bicarbonate (2×100 ml) and water (3×50 ml), dried (sodium sulfate) and evaporated to a yellow semi-crystalline residue. Two recrystallizations from ethyl acetate-petroleum ether yielded yellow plates, 10.29 g, melting point 99°-102° C., plus an additional crop of 1.33 g, melting point 97.5°-101° C. A portion was recrystallized once more giving the analytical sample, melting point 102°-103° C. maintaining the reaction temperature below -12° C After the addition quickly filtered Approximately one-fourth of the filtrate was transferred to a separatory funnel (the remainder kept chilled) and added rapidly to a gently stirred Additional chilled portions had been added (over approximately 10 minutes) The resulting solution was stirred for 2 hours purged with nitrogen for 1 hour washed with chilled half-saturated sodium bicarbonate (2×100 ml) and water (3×50 ml) dried (sodium sulfate) evaporated to a yellow semi-crystalline residue Two recrystallizations from ethyl acetate-petroleum ether yielded yellow plates, 10.29 g, melting point 99°-102° C. A portion was recrystallized once more giving the analytical sample, melting point 102°-103° C.