(2R,4R)-N-Boc-4-hydroxy-2-methylpyrrolidine

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

Procedure: To a solution of (2R,4R)-1-(tert-butoxycarbonyl)-4-hydroxy-2-methylpyrrolidine (1.92 g) and methanesulfonyl chloride (955 μl) in dichloromethane (30 ml) was added dropwise triethylamine (1.99 ml) at 0° C. After one hour, the reaction mixture was washed in turn with 1N-hydrochloric acid and brine and the organic layer was dried over magnesium sulfate. Evaporation of the solvent gave an oil, which was chromatographed on silica gel (200 ml) eluting with a mixture of hexane and ethyl acetate (1:1, V/V) to give (2R,4R)-1-(tert-butoxycarbonyl)-4-methanesulfonyloxy-2-methylpyrrolidine (2.49 g). the reaction mixture was washed in turn with 1N-hydrochloric acid and brine the organic layer was dried over magnesium sulfate Evaporation of the solvent gave an oil, which was chromatographed on silica gel (200 ml) eluting with a mixture of hexane and ethyl acetate (1:1, V/V)

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

Procedure: To a solution of (2R,4R)-1-(tert-butoxycarbonyl)-4-hydroxy-2-methylpyrrolidine (1.92 g) and methanesulfonyl chloride (955 μl) in dichloromethane (30 ml) was added dropwise triethylamine (1.99 ml) at 0° C. After one hour, the reaction mixture was washed in turn with 1N-hydrochloric acid and brine and the organic layer was dried over magnesium sulfate. Evaporation of the solvent gave an oil, which was chromatographed on silica gel (200 ml) eluting with a mixture of hexane and ethyl acetate (1:1, V/V) to give (2R,4R)-1-(tert-butoxycarbonyl)-4-methanesulfonyloxy-2-methylpyrrolidine (2.49 g). the reaction mixture was washed in turn with 1N-hydrochloric acid and brine the organic layer was dried over magnesium sulfate Evaporation of the solvent gave an oil, which was chromatographed on silica gel (200 ml) eluting with a mixture of hexane and ethyl acetate (1:1, V/V)

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

Procedure: A solution of (2R,4R)-4-(tert-butyldimethylsilyloxy)-1-(tert-butoxycarbonyl)-2-methylpyrrolidine (3.9 g) and tetrabutylammonium fluoride (1 Mol-tetrahydrofuran solution, 12.4 ml) in tetrahydrofuran (40 ml) was stirred at 0° C. for one hour. The reaction mixture was extracted with ethyl acetate, the organic layer was separated, washed with brine, and dried over magnesium sulfate. Evaporation of the solvent gave an oil, which was chromatographed on silica gel (200 ml) eluting with a mixture of hexane and ethyl acetate (1:1, V/V) to give (2R,4R)-1-(tert-butoxycarbonyl)-4-hydroxy-2-methylpyrrolidine (1.96 g). The reaction mixture was extracted with ethyl acetate the organic layer was separated washed with brine dried over magnesium sulfate Evaporation of the solvent gave an oil, which was chromatographed on silica gel (200 ml) eluting with a mixture of hexane and ethyl acetate (1:1, V/V)

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

Procedure: To a solution of 1.02 g of (2R,4R)-1-(t-butoxycarbonyl)-4-hydroxy-2-methylpyrrolidine (J. Med. Chem., 1988, 31, 1598-1611) in 10 ml of anhydrous dichloromethane, 1.7 ml of triethylamine and 1.16 g of p-toluenesulfonyl chloride were added, and then the mixture was stirred at room temperature overnight. The reaction solution was mixed with water, and followed by extraction with ethyl acetate twice. The organic layers were combined, washed in turn with water, 1N hydrochloric acid and a 1N aqueous sodium hydroxide solution and dried over anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography to obtain 1.54 g of the objective compound as a colorless oily product. followed by extraction with ethyl acetate twice washed in turn with water, 1N hydrochloric acid a 1N aqueous sodium hydroxide solution and dried over anhydrous sodium sulfate the solvent was distilled off under reduced pressure The residue was purified by silica gel column chromatography

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

Procedure: To a solution of 1.02 g of (2R,4R)-1-(t-butoxycarbonyl)-4-hydroxy-2-methylpyrrolidine (J. Med. Chem., 1988, 31, 1598-1611) in 10 ml of anhydrous dichloromethane, 1.7 ml of triethylamine and 1.16 g of p-toluenesulfonyl chloride were added, and then the mixture was stirred at room temperature overnight. The reaction solution was mixed with water, and followed by extraction with ethyl acetate twice. The organic layers were combined, washed in turn with water, 1N hydrochloric acid and a 1N aqueous sodium hydroxide solution and dried over anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography to obtain 1.54 g of the objective compound as a colorless oily product. followed by extraction with ethyl acetate twice washed in turn with water, 1N hydrochloric acid a 1N aqueous sodium hydroxide solution and dried over anhydrous sodium sulfate the solvent was distilled off under reduced pressure The residue was purified by silica gel column chromatography

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

Procedure: To a solution of (2R,4R)-1-(tert-butoxycarbonyl)-4-hydroxy-2-methylpyrrolidine (1.92 g) and methanesulfonyl chloride (955 μl) in dichloromethane (30 ml) was added dropwise triethylamine (1.99 ml) at 0° C. After one hour, the reaction mixture was washed in turn with 1N-hydrochloric acid and brine and the organic layer was dried over magnesium sulfate. Evaporation of the solvent gave an oil, which was chromatographed on silica gel (200 ml) eluting with a mixture of hexane and ethyl acetate (1:1, V/V) to give (2R,4R)-1-(tert-butoxycarbonyl)-4-methanesulfonyloxy-2-methylpyrrolidine (2.49 g). the reaction mixture was washed in turn with 1N-hydrochloric acid and brine the organic layer was dried over magnesium sulfate Evaporation of the solvent gave an oil, which was chromatographed on silica gel (200 ml) eluting with a mixture of hexane and ethyl acetate (1:1, V/V)

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

Procedure: A solution of (2R,4R)-4-(tert-butyldimethylsilyloxy)-1-(tert-butoxycarbonyl)-2-methylpyrrolidine (3.9 g) and tetrabutylammonium fluoride (1 Mol-tetrahydrofuran solution, 12.4 ml) in tetrahydrofuran (40 ml) was stirred at 0° C. for one hour. The reaction mixture was extracted with ethyl acetate, the organic layer was separated, washed with brine, and dried over magnesium sulfate. Evaporation of the solvent gave an oil, which was chromatographed on silica gel (200 ml) eluting with a mixture of hexane and ethyl acetate (1:1, V/V) to give (2R,4R)-1-(tert-butoxycarbonyl)-4-hydroxy-2-methylpyrrolidine (1.96 g). The reaction mixture was extracted with ethyl acetate the organic layer was separated washed with brine dried over magnesium sulfate Evaporation of the solvent gave an oil, which was chromatographed on silica gel (200 ml) eluting with a mixture of hexane and ethyl acetate (1:1, V/V)

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

Procedure: To a solution of 1.02 g of (2R,4R)-1-(t-butoxycarbonyl)-4-hydroxy-2-methylpyrrolidine (J. Med. Chem., 1988, 31, 1598-1611) in 10 ml of anhydrous dichloromethane, 1.7 ml of triethylamine and 1.16 g of p-toluenesulfonyl chloride were added, and then the mixture was stirred at room temperature overnight. The reaction solution was mixed with water, and followed by extraction with ethyl acetate twice. The organic layers were combined, washed in turn with water, 1N hydrochloric acid and a 1N aqueous sodium hydroxide solution and dried over anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography to obtain 1.54 g of the objective compound as a colorless oily product. followed by extraction with ethyl acetate twice washed in turn with water, 1N hydrochloric acid a 1N aqueous sodium hydroxide solution and dried over anhydrous sodium sulfate the solvent was distilled off under reduced pressure The residue was purified by silica gel column chromatography