1-O-benzyl 2-O-methyl 4-hydroxypiperidine-1,2-dicarboxylate

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a 500 ml flask, flamed dry under N2 was added CH2Cl2 (65 mL) followed by oxalyl chloride (5.2 mL, 59.6 mmol). After cooling the reaction mixture to −78° C., dimethyl sulfoxide (8.4 mL, 118.4 mmol) was added, followed by 1-benzyl 2-methyl 4-hydroxypiperidine-1,2-dicarboxylate, 13b, (8.6 g, 29.2 mmol) in CH2Cl2 (65 mL). The reaction was allowed to stir at −78° C. for 45 min. To the mixture was added triethylamine (24.4 mL, 175.1 mmol) and the mixture was allowed to warm to room temperature. The reaction mixture was diluted with CH2Cl2 and 1N HCl. The layers were separated and the aqueous phase was re-extracted with CH2Cl2. The combined organic phases were washed with water, dried over MgSO4, filtered and evaporated to dryness. The crude was purified by silica gel chromatography (30-50% EtOAc/hexanes) to give the desired product, 13c. To a 500 ml flask, flamed dry under N2 was added CH2Cl2 (65 mL) to warm to room temperature The layers were separated the aqueous phase was re-extracted with CH2Cl2 The combined organic phases were washed with water dried over MgSO4 filtered evaporated to dryness The crude was purified by silica gel chromatography (30-50% EtOAc/hexanes)

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a 500 ml flask, flamed dry under N2 was added CH2Cl2 (65 mL) followed by oxalyl chloride (5.2 mL, 59.6 mmol). After cooling the reaction mixture to −78° C., dimethyl sulfoxide (8.4 mL, 118.4 mmol) was added, followed by 1-benzyl 2-methyl 4-hydroxypiperidine-1,2-dicarboxylate, 13b, (8.6 g, 29.2 mmol) in CH2Cl2 (65 mL). The reaction was allowed to stir at −78° C. for 45 min. To the mixture was added triethylamine (24.4 mL, 175.1 mmol) and the mixture was allowed to warm to room temperature. The reaction mixture was diluted with CH2Cl2 and 1N HCl. The layers were separated and the aqueous phase was re-extracted with CH2Cl2. The combined organic phases were washed with water, dried over MgSO4, filtered and evaporated to dryness. The crude was purified by silica gel chromatography (30-50% EtOAc/hexanes) to give the desired product, 13c. To a 500 ml flask, flamed dry under N2 was added CH2Cl2 (65 mL) to warm to room temperature The layers were separated the aqueous phase was re-extracted with CH2Cl2 The combined organic phases were washed with water dried over MgSO4 filtered evaporated to dryness The crude was purified by silica gel chromatography (30-50% EtOAc/hexanes)

Conditions: temp:5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a cold (5° C.) solution of methyl 4-hydroxypiperidine-2-carboxylate, 13a, (5.17 g, 32.48 mmol) and triethylamine (6.00 mL, 43.05 mmol) in CH2Cl2 (135 mL) was added dropwise benzyl chloroformate (6.20 mL, 43.43 mmol) over 10 min. The resulting solution was stirred at 5° C. for 1 hour and then allowed to warm to room temperature. The reaction mixture was diluted with water and the layers were separated. The aqueous was re-extracted with CH2Cl2 and the combined organics were dried over MgSO4, filtered and evaporated to dryness. The crude was passed through a plug of silica gel, eluting with 30-80% EtOAc/Hexanes to afford the desired product, 13b. to warm to room temperature the layers were separated The aqueous was re-extracted with CH2Cl2 the combined organics were dried over MgSO4 filtered evaporated to dryness eluting with 30-80% EtOAc/Hexanes

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a 500 ml flask, flamed dry under N2 was added CH2Cl2 (65 mL) followed by oxalyl chloride (5.2 mL, 59.6 mmol). After cooling the reaction mixture to −78° C., dimethyl sulfoxide (8.4 mL, 118.4 mmol) was added, followed by 1-benzyl 2-methyl 4-hydroxypiperidine-1,2-dicarboxylate, 13b, (8.6 g, 29.2 mmol) in CH2Cl2 (65 mL). The reaction was allowed to stir at −78° C. for 45 min. To the mixture was added triethylamine (24.4 mL, 175.1 mmol) and the mixture was allowed to warm to room temperature. The reaction mixture was diluted with CH2Cl2 and 1N HCl. The layers were separated and the aqueous phase was re-extracted with CH2Cl2. The combined organic phases were washed with water, dried over MgSO4, filtered and evaporated to dryness. The crude was purified by silica gel chromatography (30-50% EtOAc/hexanes) to give the desired product, 13c. To a 500 ml flask, flamed dry under N2 was added CH2Cl2 (65 mL) to warm to room temperature The layers were separated the aqueous phase was re-extracted with CH2Cl2 The combined organic phases were washed with water dried over MgSO4 filtered evaporated to dryness The crude was purified by silica gel chromatography (30-50% EtOAc/hexanes)

Conditions: temp:5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a cold (5° C.) solution of methyl 4-hydroxypiperidine-2-carboxylate, 13a, (5.17 g, 32.48 mmol) and triethylamine (6.00 mL, 43.05 mmol) in CH2Cl2 (135 mL) was added dropwise benzyl chloroformate (6.20 mL, 43.43 mmol) over 10 min. The resulting solution was stirred at 5° C. for 1 hour and then allowed to warm to room temperature. The reaction mixture was diluted with water and the layers were separated. The aqueous was re-extracted with CH2Cl2 and the combined organics were dried over MgSO4, filtered and evaporated to dryness. The crude was passed through a plug of silica gel, eluting with 30-80% EtOAc/Hexanes to afford the desired product, 13b. to warm to room temperature the layers were separated The aqueous was re-extracted with CH2Cl2 the combined organics were dried over MgSO4 filtered evaporated to dryness eluting with 30-80% EtOAc/Hexanes

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a 500 ml flask, flamed dry under N2 was added CH2Cl2 (65 mL) followed by oxalyl chloride (5.2 mL, 59.6 mmol). After cooling the reaction mixture to −78° C., dimethyl sulfoxide (8.4 mL, 118.4 mmol) was added, followed by 1-benzyl 2-methyl 4-hydroxypiperidine-1,2-dicarboxylate, 13b, (8.6 g, 29.2 mmol) in CH2Cl2 (65 mL). The reaction was allowed to stir at −78° C. for 45 min. To the mixture was added triethylamine (24.4 mL, 175.1 mmol) and the mixture was allowed to warm to room temperature. The reaction mixture was diluted with CH2Cl2 and 1N HCl. The layers were separated and the aqueous phase was re-extracted with CH2Cl2. The combined organic phases were washed with water, dried over MgSO4, filtered and evaporated to dryness. The crude was purified by silica gel chromatography (30-50% EtOAc/hexanes) to give the desired product, 13c. To a 500 ml flask, flamed dry under N2 was added CH2Cl2 (65 mL) to warm to room temperature The layers were separated the aqueous phase was re-extracted with CH2Cl2 The combined organic phases were washed with water dried over MgSO4 filtered evaporated to dryness The crude was purified by silica gel chromatography (30-50% EtOAc/hexanes)

Conditions: temp:5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a cold (5° C.) solution of methyl 4-hydroxypiperidine-2-carboxylate, 13a, (5.17 g, 32.48 mmol) and triethylamine (6.00 mL, 43.05 mmol) in CH2Cl2 (135 mL) was added dropwise benzyl chloroformate (6.20 mL, 43.43 mmol) over 10 min. The resulting solution was stirred at 5° C. for 1 hour and then allowed to warm to room temperature. The reaction mixture was diluted with water and the layers were separated. The aqueous was re-extracted with CH2Cl2 and the combined organics were dried over MgSO4, filtered and evaporated to dryness. The crude was passed through a plug of silica gel, eluting with 30-80% EtOAc/Hexanes to afford the desired product, 13b. to warm to room temperature the layers were separated The aqueous was re-extracted with CH2Cl2 the combined organics were dried over MgSO4 filtered evaporated to dryness eluting with 30-80% EtOAc/Hexanes