Lithium Hexamethyldisilazide → 4-[2-(tert-Butyldimethylsilyloxy)-1-hydroxyethyl]-piperidine-1,4-dicarboxylic acid 1-benzyl ester 4-ethyl ester

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Reaction Steps

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%).

Provenance & Evidence