tert-butyl pyrazolidine-3-carboxylate

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of 3-pyrazolidinecarboxylic acid, 1,1-dimethylethyl ester (10.935 g., 63.5 mmol.) in dry acetonitrile (90 ml.) was cooled to 0° C. (ice-salt bath) and treated with dry pyridine (11.0 ml.) followed by a solution of benzylchloroformate (12.54 g., 10.5 ml., 69.9 mmol.) in dry acetonitrile (25 ml.). The reaction was stirred at 0° C. for 3 hours, evaporated to dryness and the syrup obtained was redissolved in ethyl acetate (250 ml.). The solution was washed with 5% sodium bicarbonate (2×25 ml.) and brine (25 ml.), dried (anhydrous sodium sulfate), filtered, evaporated to dryness and dried in vacuo. The crude product mixture was chromatographed on a silica gel column (Merck), eluting the column with ethyl acetate:hexane mixtures (1:4; 1:2) to give 11.144 g. of title product as a syrup. evaporated to dryness the syrup obtained The solution was washed with 5% sodium bicarbonate (2×25 ml.) and brine (25 ml.) dried (anhydrous sodium sulfate) filtered evaporated to dryness dried in vacuo The crude product mixture was chromatographed on a silica gel column (Merck) eluting the column with ethyl acetate hexane mixtures (1:4; 1:2) to give 11.144 g

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of 3-pyrazolidinecarboxylic acid, 1,1-dimethylethyl ester (10.935 g., 63.5 mmol.) in dry acetonitrile (90 ml.) was cooled to 0° C. (ice-salt bath) and treated with dry pyridine (11.0 ml.) followed by a solution of benzylchloroformate (12.54 g., 10.5 ml., 69.9 mmol.) in dry acetonitrile (25 ml.). The reaction was stirred at 0° C. for 3 hours, evaporated to dryness and the syrup obtained was re-dissolved in ethyl acetate (250 ml.). The solution was washed with 5% sodium bicarbonate (2×25 ml.) and brine (25 ml.), dried (anhydrous sodium sulfate), filtered, evaporated to dryness and dried in vacuo. The crude product mixture was chromatographed on a silica gel column (Merck), eluting the column with ethyl acetate:hexane mixtures (1:4; 1:2) to give 11.144 g. of title product as a syrup. TLC (ethyl acetate:hexane, 1:1) Rf =0.25. evaporated to dryness the syrup obtained The solution was washed with 5% sodium bicarbonate (2×25 ml.) and brine (25 ml.) dried (anhydrous sodium sulfate) filtered evaporated to dryness dried in vacuo The crude product mixture was chromatographed on a silica gel column (Merck) eluting the column with ethyl acetate hexane mixtures (1:4; 1:2) to give 11.144 g

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of 3-pyrazolidinecarboxylic acid, 1,1-dimethylethyl ester (10.935 g., 63.5 mmol.) in dry acetonitrile (90 ml.) was cooled to 0° C. (ice-salt bath) and treated with dry pyridine (11.0 ml.) followed by a solution of benzylchloroformate (12.54 g., 10.5 ml., 69.9 mmol.) in dry acetonitrile (25 ml.). The reaction was stirred at 0° C. for 3 hours, evaporated to dryness and the syrup obtained was re-dissolved in ethyl acetate (250 ml.). The solution was washed with 5% sodium bicarbonate (2×25 ml.) and brine (25 ml.), dried (anhydrous sodium sulfate), filtered, evaporated to dryness and dried in vacuo. The crude product mixture was chromatographed on a silica gel column (Merck), eluting the column with ethyl acetate:hexane mixtures (1:4; 1:2) to give 11.144 g. of title product as a syrup. TLC (ethyl acetate:hexane, 1:1) Rf =0.25. evaporated to dryness the syrup obtained The solution was washed with 5% sodium bicarbonate (2×25 ml.) and brine (25 ml.) dried (anhydrous sodium sulfate) filtered evaporated to dryness dried in vacuo The crude product mixture was chromatographed on a silica gel column (Merck) eluting the column with ethyl acetate hexane mixtures (1:4; 1:2) to give 11.144 g

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of 3-pyrazolidinecarboxylic acid, 1,1-dimethylethyl ester (10.935 g., 63.5 mmol.) in dry acetonitrile (90 ml.) was cooled to 0° C. (ice-salt bath) and treated with dry pyridine (11.0 ml.) followed by a solution of benzylchloroformate (12.54 g., 10.5 ml., 69.9 mmol.) in dry acetonitrile (25 ml.). The reaction was stirred at 0° C. for 3 hours, evaporated to dryness and the syrup obtained was redissolved in ethyl acetate (250 ml.). The solution was washed with 5% sodium bicarbonate (2×25 ml.) and brine (25 ml.), dried (anhydrous sodium sulfate), filtered, evaporated to dryness and dried in vacuo. The crude product mixture was chromatographed on a silica gel column (Merck), eluting the column with ethyl acetate:hexane mixtures (1:4; 1:2) to give 11.144 g. of title product as a syrup. TLC(ethyl acetate:hexane, 1:1) Rf =0.25. evaporated to dryness the syrup obtained The solution was washed with 5% sodium bicarbonate (2×25 ml.) and brine (25 ml.) dried (anhydrous sodium sulfate) filtered evaporated to dryness dried in vacuo The crude product mixture was chromatographed on a silica gel column (Merck) eluting the column with ethyl acetate hexane mixtures (1:4; 1:2) to give 11.144 g

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of 3-pyrazolidinecarboxylic acid, 1,1-dimethylethyl ester (10.935 g., 63.5 mmol.) in dry acetonitrile (90 ml.) was cooled to 0° C. (ice-salt bath) and treated with dry pyridine (11.0 ml.) followed by a solution of benzylchloroformate (12.54 g., 10.5 ml., 69.9 mmol.) in dry acetonitrile (25 ml.). The reaction was stirred at 0° C. for 3 hours, evaporated to dryness and the syrup obtained was redissolved in ethyl acetate (250 ml.). The solution was washed with 5% sodium bicarbonate (2×25 ml.) and brine (25 ml.), dried (anhydrous sodium sulfate), filtered, evaporated to dryness and dried in vacuo. The crude product mixture was chromatographed on a silica gel column (Merck), eluting the column with ethyl acetate:hexane mixtures (1:4; 1:2) to give 11.144 g. of title product as a syrup. evaporated to dryness the syrup obtained The solution was washed with 5% sodium bicarbonate (2×25 ml.) and brine (25 ml.) dried (anhydrous sodium sulfate) filtered evaporated to dryness dried in vacuo The crude product mixture was chromatographed on a silica gel column (Merck) eluting the column with ethyl acetate hexane mixtures (1:4; 1:2) to give 11.144 g

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of 3-pyrazolidinecarboxylic acid, 1,1-dimethylethyl ester (10.935 g., 63.5 mmol.) in dry acetonitrile (90 ml.) was cooled to 0° C. (ice-salt bath) and treated with dry pyridine (11.0 ml.) followed by a solution of benzylchloroformate (12.54 g., 10.5 ml., 69.9 mmol.) in dry acetonitrile (25 ml.). The reaction was stirred at 0° C. for 3 hours, evaporated to dryness and the syrup obtained was redissolved in ethyl acetate (250 ml.). The solution was washed with 5% sodium bicarbonate (2×25 ml.) and brine (25 ml.), dried (anhydrous sodium sulfate), filtered, evaporated to dryness and dried in vacuo. The crude product mixture was chromatographed on a silica gel column (Merck), eluting the column with ethyl acetate:hexane mixtures (1:4; 1:2) to give 11.144 g. of title product as a syrup. evaporated to dryness the syrup obtained The solution was washed with 5% sodium bicarbonate (2×25 ml.) and brine (25 ml.) dried (anhydrous sodium sulfate) filtered evaporated to dryness dried in vacuo The crude product mixture was chromatographed on a silica gel column (Merck) eluting the column with ethyl acetate hexane mixtures (1:4; 1:2) to give 11.144 g

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of 3-pyrazolidinecarboxylic acid, 1,1-dimethylethyl ester (10.935 g., 63.5 mmol.) in dry acetonitrile (90 ml.) was cooled to 0° C. (ice-salt bath) and treated with dry pyridine (11.0 ml.) followed by a solution of benzylchloroformate (12.54 g., 10.5 ml., 69.9 mmol.) in dry acetonitrile (25 ml.). The reaction was stirred at 0° C. for 3 hours, evaporated to dryness and the syrup obtained was re-dissolved in ethyl acetate (250 ml.). The solution was washed with 5% sodium bicarbonate (2×25 ml.) and brine (25 ml.), dried (anhydrous sodium sulfate), filtered, evaporated to dryness and dried in vacuo. The crude product mixture was chromatographed on a silica gel column (Merck), eluting the column with ethyl acetate:hexane mixtures (1:4; 1:2) to give 11.144 g. of title product as a syrup. TLC (ethyl acetate:hexane, 1:1) Rf =0.25. evaporated to dryness the syrup obtained The solution was washed with 5% sodium bicarbonate (2×25 ml.) and brine (25 ml.) dried (anhydrous sodium sulfate) filtered evaporated to dryness dried in vacuo The crude product mixture was chromatographed on a silica gel column (Merck) eluting the column with ethyl acetate hexane mixtures (1:4; 1:2) to give 11.144 g

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of 3-pyrazolidinecarboxylic acid, 1,1-dimethylethyl ester (10.935 g., 63.5 mmol.) in dry acetonitrile (90 ml.) was cooled to 0° C. (ice-salt bath) and treated with dry pyridine (11.0 ml.) followed by a solution of benzylchloroformate (12.54 g., 10.5 ml., 69.9 mmol.) in dry acetonitrile (25 ml.). The reaction was stirred at 0° C. for 3 hours, evaporated to dryness and the syrup obtained was redissolved in ethyl acetate (250 ml.). The solution was washed with 5% sodium bicarbonate (2×25 ml.) and brine (25 ml.), dried (anhydrous sodium sulfate), filtered, evaporated to dryness and dried in vacuo. The crude product mixture was chromatographed on a silica gel column (Merck), eluting the column with ethyl acetate:hexane mixtures (1:4; 1:2) to give 11.144 g. of title product as a syrup. evaporated to dryness the syrup obtained The solution was washed with 5% sodium bicarbonate (2×25 ml.) and brine (25 ml.) dried (anhydrous sodium sulfate) filtered evaporated to dryness dried in vacuo The crude product mixture was chromatographed on a silica gel column (Merck) eluting the column with ethyl acetate hexane mixtures (1:4; 1:2) to give 11.144 g

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of 3-pyrazolidinecarboxylic acid, 1,1-dimethylethyl ester (10.935 g., 63.5 mmol.) in dry acetonitrile (90 ml.) was cooled to 0° C. (ice-salt bath) and treated with dry pyridine (11.0 ml.) followed by a solution of benzylchloroformate (12.54 g., 10.5 ml., 69.9 mmol.) in dry acetonitrile (25 ml.). The reaction was stirred at 0° C. for 3 hours, evaporated to dryness and the syrup obtained was redissolved in ethyl acetate (250 ml.). The solution was washed with 5% sodium bicarbonate (2×25 ml.) and brine (25 ml.), dried (anhydrous sodium sulfate), filtered, evaporated to dryness and dried in vacuo. The crude product mixture was chromatographed on a silica gel column (Merck), eluting the column with ethyl acetate:hexane mixtures (1:4; 1:2) to give 11.144 g. of title product as a syrup. evaporated to dryness the syrup obtained The solution was washed with 5% sodium bicarbonate (2×25 ml.) and brine (25 ml.) dried (anhydrous sodium sulfate) filtered evaporated to dryness dried in vacuo The crude product mixture was chromatographed on a silica gel column (Merck) eluting the column with ethyl acetate hexane mixtures (1:4; 1:2) to give 11.144 g

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: At 0° C., to a 50 mL round bottomed flask charged with 1,1-dimethylethyl 3-pyrazolidinecarboxylate (0.054 g, 0.259 mmol) and stirrer in dichloromethane (DCM) (3 mL), was added triethylamine (0.079 mL, 0.569 mmol). After a couple of minutes, N-(benzyloxycarbonyloxy)succinimide (CBz-OSu) (0.064 g, 0.259 mmol) in dichloromethane (DCM) (1.5 mL) was added dropwise. The reaction mixture stirred at 0° C. for one hour, then warmed to r.t. After 2 hr at r.t., the solvent was evaporated and the residue was dissolved in EtOAc (30 mL), washed with water (15 mL×2), sat. NaHCO3 (15 ml), brine (15 mL), dried over Na2SO4 and concentrated to afford the crude product as a colorless gum (88 mg). After a couple of minutes warmed to r.t After 2 hr at r.t. the solvent was evaporated the residue was dissolved in EtOAc (30 mL) washed with water (15 mL×2), sat. NaHCO3 (15 ml), brine (15 mL) dried over Na2SO4 concentrated

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

实验步骤: 3-(1,1-Dimethylethyl) 1,2-bis(phenylmethyl) 1,2,3-pyrazolidinetricarboxylate (5.30 g, 12.03 mmol) was dissolved in methanol (100 mL) and 10% Pd/C (degussa type) (1.06 g, 0.996 mmol) was added. The mixture was stirred under a balloon of hydrogen for 60 min. LCMS showed clean deprotection. HCl in ether (6.02 mL, 12.03 mmol) was added, and the mixture was stirred 5 min. The catalyst was filtered off and the filtrate was evaporated, yielding 1,1-dimethylethyl 3-pyrazolidinecarboxylate.HCl (2.45 g, 11.74 mmol, 98% yield) as an orange solid. The catalyst was filtered off the filtrate was evaporated

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of 3-pyrazolidinecarboxylic acid, 1,1-dimethylethyl ester (10.935 g., 63.5 mmol.) in dry acetonitrile (90 ml.) was cooled to 0° C. (ice-salt bath) and treated with dry pyridine (11.0 ml.) followed by a solution of benzylchloroformate (12.54 g., 10.5 ml., 69.9 mmol.) in dry acetonitrile (25 ml.). The reaction was stirred at 0° C. for 3 hours, evaporated to dryness and the syrup obtained was redissolved in ethyl acetate (250 ml.). The solution was washed with 5% sodium bicarbonate (2×25 ml.) and brine (25 ml.), dried (anhydrous sodium sulfate), filtered, evaporated to dryness and dried in vacuo. The crude product mixture was chromatographed on a silica gel column (Merck), eluting the column with ethyl acetate:hexane mixtures (1:4; 1:2) to give 11.144 g. of title product as a syrup. evaporated to dryness the syrup obtained The solution was washed with 5% sodium bicarbonate (2×25 ml.) and brine (25 ml.) dried (anhydrous sodium sulfate) filtered evaporated to dryness dried in vacuo The crude product mixture was chromatographed on a silica gel column (Merck) eluting the column with ethyl acetate hexane mixtures (1:4; 1:2) to give 11.144 g