(2S)-1-prop-2-enoxycarbonylpyrrolidine-2-carboxylic acid

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

Procedure: To a solution of (2S)-1-allyloxycarbonyl-2-carboxypyrrolidine (72.4 g) in N,N-dimethylformamide (250 ml) were added potassium carbonate (57.6 g) and methyl iodide (43.2 ml) at 0° C. with stirring. The resulting mixture was allowed to warm to ambient temperature and stirring was continued for additional 1 hour. The reaction mixture was taken up into a mixture of ethyl acetate (1.2 l) and water (0.6 l). The organic layer was separated, washed in turn with water (1l×3), brine (1l), dried over magnesium sulfate, and evaporated to give (2S)-1-allyloxycarbonyl-2-methoxycarbonylpyrrolidine (66.21 g). stirring The organic layer was separated washed in turn with water (1l×3), brine (1l) dried over magnesium sulfate evaporated

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

Procedure: To a suspension of (2S)-2-carboxypyrrolidine (40 g) in a mixture of water (200 ml) and tetrahydrofuran (200 ml) was added a solution of allyl chloroformate (44 ml) in tetrahydrofuran (40 ml) at 0° C. while adjusting pH to around 9 with 4N aqueous sodium hydroxide. After stirring at 0° C. for 1 hour at pH 9, the aqueous layer was saturated with sodium chloride, and the mixture was diluted with ethyl acetate (200 ml). The aqueous layer was separated and washed with ethyl acetate. After adjusting pH to around 2 with 6N hydrochloric acid, the mixture was extracted with two portions of ethyl acetate (200 ml×2). The combined extract was dried over magnesium sulfate and evaporated in vacuo to give (2S)-1-allyloxycarbonyl-2-carboxypyrrolidine (72.49 g). The aqueous layer was separated washed with ethyl acetate the mixture was extracted with two portions of ethyl acetate (200 ml×2) The combined extract was dried over magnesium sulfate evaporated in vacuo

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

Procedure: To a solution of (2S)-1-allyloxycarbonyl-2-carboxypyrrolidine (10 g) in dichloromethane (100 ml) were added dicyclohexylcarbodiimide (9.8 g), Meldrum's acid (6.8 g) and 4-dimethylaminopyridine (5.8 g) at 0° C. After stirring for 24 hours at ambient temperature, the resulting precipitate was removed by filtration. The filtrate was washed with 1N hydrochloric acid solution, evaporated in vacuo. The residue was dissolved in a mixture of acetic acid (80 ml) and water (60 ml), and refluxed for 1 hour. Evaporation of the solvent gave a residue, which was taken up into ethyl acetate. The solution was washed in turn with saturated sodium bicarbonate and brine, dried over magnesium sulfate, and evaporated. The residue was chromatographed on silica gel eluting with a mixture of n-hexane and ethyl acetate (2:1, V/V) to give (2S)-2-acetyl-1-allyloxycarbonylpyrrolidine (4.1 g). the resulting precipitate was removed by filtration The filtrate was washed with 1N hydrochloric acid solution evaporated in vacuo The residue was dissolved in a mixture of acetic acid (80 ml) and water (60 ml) refluxed for 1 hour Evaporation of the solvent gave a residue, which The solution was washed in turn with saturated sodium bicarbonate and brine dried over magnesium sulfate evaporated The residue was chromatographed on silica gel eluting with a mixture of n-hexane and ethyl acetate (2:1, V/V)

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

Procedure: To a solution of (2S)-1-allyloxycarbonyl-2-carboxypyrrolidine (10 g) in dichloromethane (100 ml) were added dicyclohexylcarbodiimide (9.8 g), Meldrum's acid (6.8 g) and 4-dimethylaminopyridine (5.8 g) at 0° C. After stirring for 24 hours at ambient temperature, the resulting precipitate was removed by filtration. The filtrate was washed with 1N hydrochloric acid solution, evaporated in vacuo. The residue was dissolved in a mixture of acetic acid (80 ml) and water (60 ml), and refluxed for 1 hour. Evaporation of the solvent gave a residue, which was taken up into ethyl acetate. The solution was washed in turn with saturated sodium bicarbonate and brine, dried over magnesium sulfate, and evaporated. The residue was chromatographed on silica gel eluting with a mixture of n-hexane and ethyl acetate (2:1, V/V) to give (2S)-2-acetyl-1-allyloxycarbonylpyrrolidine (4.1 g). the resulting precipitate was removed by filtration The filtrate was washed with 1N hydrochloric acid solution evaporated in vacuo The residue was dissolved in a mixture of acetic acid (80 ml) and water (60 ml) refluxed for 1 hour Evaporation of the solvent gave a residue, which The solution was washed in turn with saturated sodium bicarbonate and brine dried over magnesium sulfate evaporated The residue was chromatographed on silica gel eluting with a mixture of n-hexane and ethyl acetate (2:1, V/V)

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

Procedure: To a solution of (2S)-1-allyloxycarbonyl-2-carboxypyrrolidine (72.4 g) in N,N-dimethylformamide (250 ml) were added potassium carbonate (57.6 g) and methyl iodide (43.2 ml) at ° C. with stirring. The resulting mixture was allowed to warm to ambient temperature and stirring was continued for additional 1 hour. The reaction mixture was taken up into a mixture of ethyl acetate (1.2 l) and water (0.6 l). The organic layer was separated, washed in turn with water (1l×3), brine (1l), dried over magnesium sulfate, and evaporated to give (2S)-1-allyloxycarbonyl-2-methoxycarbonylpyrrolidine (66.21 g). stirring The organic layer was separated washed in turn with water (1l×3), brine (1l) dried over magnesium sulfate evaporated

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

Procedure: To a suspension of (2S)-2-carboxypyrrolidine (40 g) in a mixture of water (200 ml) and tetrahydrofuran (200 ml) was added a solution of allyl chloroformate (44 ml) in tetrahydrofuran (40 ml) at ° C. while adjusting pH to around 9 with 4N aqueous sodium hydroxide. After stirring at ° C. for 1 hour at pH 9, the aqueous layer was saturated with sodium chloride, and the mixture was diluted with ethyl acetate (200 ml). The aqueous layer was separated and washed with ethyl acetate. After adjusting pH to around 2 with 6N hydrochloric acid, the mixture was extracted with two portions of ethyl acetate (200 ml×2). The combined extract was dried over magnesium sulfate and evaporated in vacuo to give (2S)-1-allyloxycarbonyl-2-carboxypyrrolidine (72.49 g). The aqueous layer was separated washed with ethyl acetate the mixture was extracted with two portions of ethyl acetate (200 ml×2) The combined extract was dried over magnesium sulfate evaporated in vacuo

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

Procedure: To a solution of (2S)-1-allyloxycarbonyl-2-carboxypyrrolidine (72.4 g) in N,N-dimethylformamide (250 ml) were added potassium carbonate (57.6 g) and methyl iodide (43.2 ml) at 0° C. with stirring. The resulting mixture was allowed to warm to ambient temperature and stirring was continued for additional 1 hour. The reaction mixture was taken up into a mixture of ethyl acetate (1.2 l) and water (0.6 l). The organic layer was separated, washed in turn with water (1l×3), brine (1l), dried over magnesium sulfate, and evaporated to give (2S)-1-allyloxycarbonyl-2-methoxycarbonylpyrrolidine (66.21 g). stirring The organic layer was separated washed in turn with water (1l×3), brine (1l) dried over magnesium sulfate evaporated

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

Procedure: To a suspension of (2S)-2-carboxypyrrolidine (40 g) in a mixture of water (200 ml) and tetrahydrofuran (200 ml) was added a solution of allyl chloroformate (44 ml) in tetrahydrofuran (40 ml) at 0° C. while adjusting pH to around 9 with 4N aqueous sodium hydroxide. After stirring at 0° C. for 1 hour at pH 9, the aqueous layer was saturated with sodium chloride, and the mixture was diluted with ethyl acetate (200 ml). The aqueous layer was separated and washed with ethyl acetate. After adjusting pH to around 2 with 6N hydrochloric acid, the mixture was extracted with two portions of ethyl acetate (200 ml×2). The combined extract was dried over magnesium sulfate and evaporated in vacuo to give (2S)-1-allyloxycarbonyl-2-carboxypyrrolidine (72.49 g). The aqueous layer was separated washed with ethyl acetate the mixture was extracted with two portions of ethyl acetate (200 ml×2) The combined extract was dried over magnesium sulfate evaporated in vacuo

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

Procedure: To a solution of (2S)-1-allyloxycarbonyl-2-carboxypyrrolidine (10 g) in dichloromethane (100 ml) were added dicyclohexylcarbodiimide (9.8 g), Meldrum's acid (6.8 g) and 4-dimethylaminopyridine (5.8 g) at 0° C. After stirring for 24 hours at ambient temperature, the resulting precipitate was removed by filtration. The filtrate was washed with 1N hydrochloric acid solution, evaporated in vacuo. The residue was dissolved in a mixture of acetic acid (80 ml) and water (60 ml), and refluxed for 1 hour. Evaporation of the solvent gave a residue, which was taken up into ethyl acetate. The solution was washed in turn with saturated sodium bicarbonate and brine, dried over magnesium sulfate, and evaporated. The residue was chromatographed on silica gel eluting with a mixture of n-hexane and ethyl acetate (2:1, V/V) to give (2S)-2-acetyl-1-allyloxycarbonylpyrrolidine (4.1 g). the resulting precipitate was removed by filtration The filtrate was washed with 1N hydrochloric acid solution evaporated in vacuo The residue was dissolved in a mixture of acetic acid (80 ml) and water (60 ml) refluxed for 1 hour Evaporation of the solvent gave a residue, which The solution was washed in turn with saturated sodium bicarbonate and brine dried over magnesium sulfate evaporated The residue was chromatographed on silica gel eluting with a mixture of n-hexane and ethyl acetate (2:1, V/V)