反应详情

温度

0 °C

To a solution of triphenylphosphine (1.11 g, 4.23 mmol) in THF (20 ml) at 0° C. was added diisopropyl azodicarboxylate (0.83 ml, 0.85 g, 4.24 mmol) dropwise and the resulting precipitate was stirred at 0° C. for 30 minutes. 4-{Hydroxy-[2-(2,4,6-trimethyl-phenyl)-acetyl]-amino}-1-methoxy-piperidine-4-carboxylic acid methyl ester (compound P3ii.3 obtained in analogy to preparation example 11, step 4) (1.3 g, 3.57 mmol) was further added in one portion, followed by a solution of 1-methoxy-piperidin-4-ol (0.53 g, 4.04 mmol) in THF (6 ml) dropwise at 0° C. The reaction mixture was stirred at room temperature for two hours and concentrated in vacuo. The residue was triturated with hexane and filtered to remove part of the insoluble triphenylphosphine oxide. The filtrate was evaporated and the residue purified by chromatography on silica gel (gradient ethyl acetate/heptane 3:7→ethyl acetate). Yield: 861 mg of pure 1-methoxy-4-{(1-methoxy-piperidin-4-yloxy)-[2-(2,4,6-trimethyl-phenyl)-acetyl]-amino}-piperidine-4-carboxylic acid methyl ester (title compound P3ii.26) as a colorless gum, followed by a second fraction of compound P3ii.26 (701 mg) slightly contaminated with triphenylphosphine oxide.

1. stirringThe reaction mixture was stirred at room temperature for two hours
2. concentrationconcentrated in vacuo
3. customThe residue was triturated with hexane
4. filtrationfiltered
5. customto remove part of the insoluble triphenylphosphine oxide
6. customThe filtrate was evaporated
7. customthe residue purified by chromatography on silica gel (gradient ethyl acetate/heptane 3:7→ethyl acetate)