反应详情

A solution of piperidine-1,4-dicarboxylic acid 1-benzyl ester 4-ethyl ester (Description 1; 10 g, 34.4 mmol) in tetrahydrofuran (100 ml) was cooled to −78° C. Lithium bis(trimethylsilyl)amide (1.0M in tetrahydrofuran, 50 ml, 50 mmol) was added dropwise and the mixture stirred, allowing to warm to room temperature over 1.5 hours. The orange solution was re-cooled to −78° C. and (tert-butyldimethylsilyloxy)acetaldehyde (10 g, 57.3 mmol) added. The mixture was allowed to warm to room temperature over 2.5 hours, then quenched with saturated aqueous ammonium chloride solution. The reaction mixture was partitioned between diethyl ether and water. The organic layer was dried (MgSO4) and concentrated in vacuo. The residue was purified by flash column chromatography on silica, eluting with 5-15% diethyl ether/dichloromethane, to give the title compound (12.4 g, 78%).

1. temperatureThe orange solution was re-cooled to −78° C.
2. temperatureto warm to room temperature over 2.5 hours
3. customquenched with saturated aqueous ammonium chloride solution
4. customThe reaction mixture was partitioned between diethyl ether and water
5. dry with materialThe organic layer was dried (MgSO4)
6. concentrationconcentrated in vacuo
7. customThe residue was purified by flash column chromatography on silica
8. washeluting with 5-15% diethyl ether/dichloromethane