1-O-benzyl 2-O-methyl (2S,5R)-5-hydroxypiperidine-1,2-dicarboxylate

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

Procedure: To a solution of 2.46 g (8.39 mmol) of (2S,5R)-1-benzyloxycarbonyl-5-hydroxy-2-methoxycarbonylpiperidine in 100 ml of methanol was added 500 mg of 5% palladium-carbon, and the mixture was hydrogenated for 2 hours at atmospheric pressure and room temperature. The catalyst was removed by filtration, and the filtrate was concentrated. The residue was dissolved in 20 ml of dichloromethane. To this solution was dropwise added 1.3 ml (9.33 mmol) or triethylamine followed by 0.98 ml (9.24 mmol) of allyl chloroformate. After stirring for 2 hours, 1.3 ml (9.33 mmol) of triethylamine and 0.98 ml (9.24 mmol) of allyl chloroformate were additionally added to the mixtures, which was stirred for 1 hours. To the mixture was added 200 ml of ethyl acetate, the organic layer was washed successively with water, 1N potassium bisulfate, water, saturated aqueous sodium bicarbonate, water and saturated aqueous sodium chloride. After drying over anhydrous sodium sulfate, the solvent was removed. The residue was purified by silica gel column chromatography (Wakogel®C-300, elution with ethyl acetate - hexane system) to give 1.14 g (yield: 55 %) of the title compound. The catalyst was removed by filtration the filtrate was concentrated The residue was dissolved in 20 ml of dichloromethane was stirred for 1 hours the organic layer was washed successively with water, 1N potassium bisulfate, water, saturated aqueous sodium bicarbonate, water and saturated aqueous sodium chloride After drying over anhydrous sodium sulfate the solvent was removed The residue was purified by silica gel column chromatography (Wakogel®C-300, elution with ethyl acetate - hexane system)

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

Procedure: To a solution of 2.46 g (8.39 mmol) of (2S,5R)-1-benzyloxycarbonyl-5-hydroxy-2-methoxycarbonylpiperidine in 100 ml of methanol was added 500 mg of 5% palladium-carbon, and the mixture was hydrogenated for 2 hours at atmospheric pressure and room temperature. The catalyst was removed by filtration, and the filtrate was concentrated. The residue was dissolved in 20 ml of dichloromethane. To this solution was dropwise added 1.3 ml (9.33 mmol) or triethylamine followed by 0.98 ml (9.24 mmol) of allyl chloroformate. After stirring for 2 hours, 1.3 ml (9.33 mmol) of triethylamine and 0.98 ml (9.24 mmol) of allyl chloroformate were additionally added to the mixtures, which was stirred for 1 hours. To the mixture was added 200 ml of ethyl acetate, the organic layer was washed successively with water, 1N potassium bisulfate, water, saturated aqueous sodium bicarbonate, water and saturated aqueous sodium chloride. After drying over anhydrous sodium sulfate, the solvent was removed. The residue was purified by silica gel column chromatography (Wakogel®C-300, elution with ethyl acetate - hexane system) to give 1.14 g (yield: 55 %) of the title compound. The catalyst was removed by filtration the filtrate was concentrated The residue was dissolved in 20 ml of dichloromethane was stirred for 1 hours the organic layer was washed successively with water, 1N potassium bisulfate, water, saturated aqueous sodium bicarbonate, water and saturated aqueous sodium chloride After drying over anhydrous sodium sulfate the solvent was removed The residue was purified by silica gel column chromatography (Wakogel®C-300, elution with ethyl acetate - hexane system)

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

Procedure: To a solution of 5.7 g (19.43 mmol) of (2S,5R)-1-benzyloxycarbonyl-5-hydroxy-2-methoxycarbonylpiperidine, which was prepared by the procedure described in P.D. Bailey et al., Tetrahedron Letters. 29, 2231 (1988), in 250 ml of methanol was added 570 mg of 5% palladium-carbon, and the mixture was hydrogenated at atmospheric pressure and room temperature for 1 hours. The catalyst was removed by filtration, and the solvent was removed. To a solution of this residue in 30 ml of dioxane was dropwise added a solution of 6.85 g (21.45 mmol) of p-nitrobenzyloxycarbonyl-4,6-dimethyl-2-mercaptopyrimidine in 50 ml of dioxane, and the mixture was stirred for 1.5 hours at room temperature. To the reaction mixture was added 300 ml of ethyl acetate, the organic layer was washed successively with 50 ml of 1N HCl(×2), 50 ml of water and saturated aqueous sodium chloride. After the extract was dried over anhydrous sodium sulfate, the solvent was removed. The residue was purified by silica gel column chromatography (Wakogel® C-300, elution with ethyl acetate - hexane system) to give 5.81 g (yield: 88%) of the title compound. The catalyst was removed by filtration the solvent was removed the organic layer was washed successively with 50 ml of 1N HCl(×2), 50 ml of water and saturated aqueous sodium chloride After the extract was dried over anhydrous sodium sulfate the solvent was removed The residue was purified by silica gel column chromatography (Wakogel® C-300, elution with ethyl acetate - hexane system)

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

Procedure: To a solution of 5.7 g (19.43 mmol) of (2S,5R)-1-benzyloxycarbonyl-5-hydroxy-2-methoxycarbonylpiperidine, which was prepared by the procedure described in P.D. Bailey et al., Tetrahedron Letters. 29, 2231 (1988), in 250 ml of methanol was added 570 mg of 5% palladium-carbon, and the mixture was hydrogenated at atmospheric pressure and room temperature for 1 hours. The catalyst was removed by filtration, and the solvent was removed. To a solution of this residue in 30 ml of dioxane was dropwise added a solution of 6.85 g (21.45 mmol) of p-nitrobenzyloxycarbonyl-4,6-dimethyl-2-mercaptopyrimidine in 50 ml of dioxane, and the mixture was stirred for 1.5 hours at room temperature. To the reaction mixture was added 300 ml of ethyl acetate, the organic layer was washed successively with 50 ml of 1N HCl(×2), 50 ml of water and saturated aqueous sodium chloride. After the extract was dried over anhydrous sodium sulfate, the solvent was removed. The residue was purified by silica gel column chromatography (Wakogel® C-300, elution with ethyl acetate - hexane system) to give 5.81 g (yield: 88%) of the title compound. The catalyst was removed by filtration the solvent was removed the organic layer was washed successively with 50 ml of 1N HCl(×2), 50 ml of water and saturated aqueous sodium chloride After the extract was dried over anhydrous sodium sulfate the solvent was removed The residue was purified by silica gel column chromatography (Wakogel® C-300, elution with ethyl acetate - hexane system)

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

Procedure: To a solution of 2.46 g (8.39 mmol) of (2S,5R)-1-benzyloxycarbonyl-5-hydroxy-2-methoxycarbonylpiperidine in 100 ml of methanol was added 500 mg of 5% palladium-carbon, and the mixture was hydrogenated for 2 hours at atmospheric pressure and room temperature. The catalyst was removed by filtration, and the filtrate was concentrated. The residue was dissolved in 20 ml of dichloromethane. To this solution was dropwise added 1.3 ml (9.33 mmol) or triethylamine followed by 0.98 ml (9.24 mmol) of allyl chloroformate. After stirring for 2 hours, 1.3 ml (9.33 mmol) of triethylamine and 0.98 ml (9.24 mmol) of allyl chloroformate were additionally added to the mixtures, which was stirred for 1 hours. To the mixture was added 200 ml of ethyl acetate, the organic layer was washed successively with water, 1N potassium bisulfate, water, saturated aqueous sodium bicarbonate, water and saturated aqueous sodium chloride. After drying over anhydrous sodium sulfate, the solvent was removed. The residue was purified by silica gel column chromatography (Wakogel®C-300, elution with ethyl acetate - hexane system) to give 1.14 g (yield: 55 %) of the title compound. The catalyst was removed by filtration the filtrate was concentrated The residue was dissolved in 20 ml of dichloromethane was stirred for 1 hours the organic layer was washed successively with water, 1N potassium bisulfate, water, saturated aqueous sodium bicarbonate, water and saturated aqueous sodium chloride After drying over anhydrous sodium sulfate the solvent was removed The residue was purified by silica gel column chromatography (Wakogel®C-300, elution with ethyl acetate - hexane system)

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

Procedure: To a solution of 5.7 g (19.43 mmol) of (2S,5R)-1-benzyloxycarbonyl-5-hydroxy-2-methoxycarbonylpiperidine, which was prepared by the procedure described in P.D. Bailey et al., Tetrahedron Letters. 29, 2231 (1988), in 250 ml of methanol was added 570 mg of 5% palladium-carbon, and the mixture was hydrogenated at atmospheric pressure and room temperature for 1 hours. The catalyst was removed by filtration, and the solvent was removed. To a solution of this residue in 30 ml of dioxane was dropwise added a solution of 6.85 g (21.45 mmol) of p-nitrobenzyloxycarbonyl-4,6-dimethyl-2-mercaptopyrimidine in 50 ml of dioxane, and the mixture was stirred for 1.5 hours at room temperature. To the reaction mixture was added 300 ml of ethyl acetate, the organic layer was washed successively with 50 ml of 1N HCl(×2), 50 ml of water and saturated aqueous sodium chloride. After the extract was dried over anhydrous sodium sulfate, the solvent was removed. The residue was purified by silica gel column chromatography (Wakogel® C-300, elution with ethyl acetate - hexane system) to give 5.81 g (yield: 88%) of the title compound. The catalyst was removed by filtration the solvent was removed the organic layer was washed successively with 50 ml of 1N HCl(×2), 50 ml of water and saturated aqueous sodium chloride After the extract was dried over anhydrous sodium sulfate the solvent was removed The residue was purified by silica gel column chromatography (Wakogel® C-300, elution with ethyl acetate - hexane system)