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

Conditions: temp:0.00; pressure:0.00; stir:

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:0.00; pressure:0.00; stir:

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

Procedure: A solution of the product of stage (ii) (5.06 g) and 1,2-ethanediol (1.06 ml) in benzene (100 ml) containing 4-toluenesulphonic acid (0.2 g) was stirred at reflux temperature under a Soxhlet cup filled with 4 Å molecular sieves for 4 h. The reaction mixture was allowed to cool to 22°, washed with 2N sodium carbonate (2×20 ml), water (20 ml) and dried. The benzene solution was evaporated in vacuo to give the title compound as an oil (5.75 g). at reflux temperature under a Soxhlet cup filled with 4 Å molecular sieves for 4 h to cool to 22° washed with 2N sodium carbonate (2×20 ml), water (20 ml) dried The benzene solution was evaporated in vacuo

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)