Benzyl (S)-1-Boc-4-oxo-2-pyrrolidinecarboxylate

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

Procedure: To a stirring solution of (S)-2-benzyl 1-tert-butyl 4-oxopyrrolidine-1,2-dicarboxylate (2.82 g, 8.8 mmol) in anhydrous tetrahydrofuran (44 mL) was added 4N HCl in 1,4-dioxane (9.3 mL) at room temperature. The mixture was stirred for 18 hours at room temperature. The product was then three times with toluene on rotovap to dryness to remove all the excess acid and further dried on a high vacuum overnight and used as is in the next step. Quantitative yield. three times with toluene on rotovap to dryness to remove all the excess acid further dried on a high vacuum overnight

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

Procedure: To a stirring solution of (S)-2-benzyl 1-tert-butyl 4-oxopyrrolidine-1,2-dicarboxylate (2.82 g, 8.8 mmol) in anhydrous tetrahydrofuran (44 mL) was added 4N HCl in 1,4-dioxane (9.3 mL) at room temperature. The mixture was stirred for 18 hours at room temperature. The product was then three times with toluene on rotovap to dryness to remove all the excess acid and further dried on a high vacuum overnight and used as is in the next step. Quantitative yield. three times with toluene on rotovap to dryness to remove all the excess acid further dried on a high vacuum overnight

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

Procedure: To a stirring solution of (S)-2-benzyl 1-tert-butyl 4-oxopyrrolidine-1,2-dicarboxylate (2.82 g, 8.8 mmol) in anhydrous tetrahydrofuran (44 mL) was added 4N HCl in 1,4-dioxane (9.3 mL) at room temperature. The mixture was stirred for 18 hours at room temperature. The product was then three times with toluene on rotovap to dryness to remove all the excess acid and further dried on a high vacuum overnight and used as is in the next step. Quantitative yield. three times with toluene on rotovap to dryness to remove all the excess acid further dried on a high vacuum overnight

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

Procedure: To a stirring solution of (S)-2-benzyl 1-tert-butyl 4-oxopyrrolidine-1,2-dicarboxylate (2.82 g, 8.8 mmol) in anhydrous tetrahydrofuran (44 mL) was added 4N HCl in 1,4-dioxane (9.3 mL) at room temperature. The mixture was stirred for 18 hours at room temperature. The product was then three times with toluene on rotovap to dryness to remove all the excess acid and further dried on a high vacuum overnight and used as is in the next step. Quantitative yield. three times with toluene on rotovap to dryness to remove all the excess acid further dried on a high vacuum overnight

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

Procedure: To a stirring solution of (S)-2-benzyl 1-tert-butyl 4-oxopyrrolidine-1,2-dicarboxylate (2.82 g, 8.8 mmol) in anhydrous tetrahydrofuran (44 mL) was added 4N HCl in 1,4-dioxane (9.3 mL) at room temperature. The mixture was stirred for 18 hours at room temperature. The product was then three times with toluene on rotovap to dryness to remove all the excess acid and further dried on a high vacuum overnight and used as is in the next step. Quantitative yield. three times with toluene on rotovap to dryness to remove all the excess acid further dried on a high vacuum overnight

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

Procedure: To a stirring solution of (S)-2-benzyl 1-tert-butyl 4-oxopyrrolidine-1,2-dicarboxylate (2.82 g, 8.8 mmol) in anhydrous tetrahydrofuran (44 mL) was added 4N HCl in 1,4-dioxane (9.3 mL) at room temperature. The mixture was stirred for 18 hours at room temperature. The product was then three times with toluene on rotovap to dryness to remove all the excess acid and further dried on a high vacuum overnight and used as is in the next step. Quantitative yield. three times with toluene on rotovap to dryness to remove all the excess acid further dried on a high vacuum overnight

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

Procedure: To a stirring solution of (S)-2-benzyl 1-tert-butyl 4-oxopyrrolidine-1,2-dicarboxylate (2.82 g, 8.8 mmol) in anhydrous tetrahydrofuran (44 mL) was added 4N HCl in 1,4-dioxane (9.3 mL) at room temperature. The mixture was stirred for 18 hours at room temperature. The product was then three times with toluene on rotovap to dryness to remove all the excess acid and further dried on a high vacuum overnight and used as is in the next step. Quantitative yield. three times with toluene on rotovap to dryness to remove all the excess acid further dried on a high vacuum overnight

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

Procedure: To a stirring solution of (S)-2-benzyl 1-tert-butyl 4-oxopyrrolidine-1,2-dicarboxylate (2.82 g, 8.8 mmol) in anhydrous tetrahydrofuran (44 mL) was added 4N HCl in 1,4-dioxane (9.3 mL) at room temperature. The mixture was stirred for 18 hours at room temperature. The product was then three times with toluene on rotovap to dryness to remove all the excess acid and further dried on a high vacuum overnight and used as is in the next step. Quantitative yield. three times with toluene on rotovap to dryness to remove all the excess acid further dried on a high vacuum overnight

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

Procedure: To a stirring solution of (S)-2-benzyl 1-tert-butyl 4-oxopyrrolidine-1,2-dicarboxylate (2.82 g, 8.8 mmol) in anhydrous tetrahydrofuran (44 mL) was added 4N HCl in 1,4-dioxane (9.3 mL) at room temperature. The mixture was stirred for 18 hours at room temperature. The product was then three times with toluene on rotovap to dryness to remove all the excess acid and further dried on a high vacuum overnight and used as is in the next step. Quantitative yield. three times with toluene on rotovap to dryness to remove all the excess acid further dried on a high vacuum overnight

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

Procedure: To a stirring solution of a mixture of (S)-1-(tert-butoxycarbonyl)-4-oxopyrrolidine-2-carboxylic acid (2.85 g, 12.43 mmol) and potassium carbonate (4.33 g, 24.87 mmol) in anhydrous N,N-dimethylformamide (60 mL) was added benzyl bromide (4.25 g, 24.87 mmol). The mixture was stirred at room temperature overnight. The resulting crude mixture was diluted with ethylacetate and the organic layer was washed with 10% sodium carbonate and brine. The organic layer was dried over sodium sulfate and volatiles were removed in-vacuo. The residue was purified on normal phase column to yield 2.82 g (71%) of desired product. the organic layer was washed with 10% sodium carbonate and brine The organic layer was dried over sodium sulfate and volatiles were removed in-vacuo The residue was purified on normal phase column

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

Procedure: To a stirring solution of a mixture of (S)-1-(tert-butoxycarbonyl)-4-oxopyrrolidine-2-carboxylic acid (2.85 g, 12.43 mmol) and potassium carbonate (4.33 g, 24.87 mmol) in anhydrous N,N-dimethylformamide (60 mL) was added benzyl bromide (4.25 g, 24.87 mmol). The mixture was stirred at room temperature overnight. The resulting crude mixture was diluted with ethylacetate and the organic layer was washed with 10% sodium carbonate and brine. The organic layer was dried over sodium sulfate and volatiles were removed in-vacuo. The residue was purified on normal phase column to yield 2.82 g (71%) of desired product. the organic layer was washed with 10% sodium carbonate and brine The organic layer was dried over sodium sulfate and volatiles were removed in-vacuo The residue was purified on normal phase column

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

Procedure: (2S,4S)-1-(tert-butoxycarbonyl)-4-ethylpyrrolidine-2-carboxylic acid: To a mixture of KOtBu (0.176 g, 1.57 mmol) and (ethyl)triphenylphosphonium bromide (0.581 g, 1.57 mmol) was added THF (3.1 mL) at rt. The mixture was stirred for 1 h. Next, a solution of (S)-2-benzyl 1-tert-butyl 4-oxopyrrolidine-1,2-dicarboxylate (0.200 g, 0.581 mmol) dissolved in THF (1 mL) was added via cannula and the flask was rinsed with THF (0.5 mL). The reaction was stirred overnight at rt. The reaction was quenched with water and diluted with EtOAc. The layers were separated and the organic layer was washed with brine, dried (MgSO4), and concentrated. The crude product was purified by silica gel chromatography to provide (S)-2-benzyl 1-tert-butyl 4-ethylidenepyrrolidine-1,2-dicarboxylate as a colorless oil as a mixture of E/Z isomers. The E/Z mixture was used directly in the next reaction. (S)-2-benzyl 1-tert-butyl 4-ethylidenepyrrolidine-1,2-dicarboxylate (0.0866 g, 0.261 mmol) was dissolved in EtOH (5.2 mL) and 10% Pd/C (0.092 g, 0.086 mmol) was added. The reaction was purged with argon and then H2 and stirred overnight under a H2 balloon. The reaction was filtered and concentrated. The crude product was purified by silica gel chromatography to provide 57A (colorless oil, 0.0358 g, 0.147 mmol, 23.5% yield). LC-MS Anal. Calc'd for C12H21NO4 243.30. found [M+H] 244.0. 1H NMR (400 MHz, chloroform-d) δ ppm 4.13-4.34 (1 H, m), 3.63-3.83 (1 H, m), 2.91-3.04 (1 H, m), 2.31-2.51 (1 H, m), 1.99-2.12 (1 H, m, J=14.31, 10.18, 7.15, 7.15 Hz), 1.54-1.82 (1 H, m), 1.33-1.51 (11 H, m), 0.91 (3 H, t, J=7.02 Hz). was added via cannula the flask was rinsed with THF (0.5 mL) The reaction was stirred overnight at rt The reaction was quenched with water diluted with EtOAc The layers were separated the organic layer was washed with brine dried (MgSO4) concentrated The crude product was purified by silica gel chromatography