反应详情

温度

-5 °C

To a solution of diisopropylamine (5.68 mL, 0.040 mol) in 100 ml THF at −78° C. was added nBuli (1.6M solution in hexane, 25.9 mL, 0.041 mol) drop-wise. The reaction mixture was warmed to −5° C. and stirring was continued for 30 mins. A solution of 1-benzylpiperidine-4-carboxylic acid ethyl ester (5.00 g, 0.020 mol) in THF (20 mL) was added drop wise and stirring was continued for a further 3 hr followed by the addition of a solution of 1-bromo-2-methoxy-ethane (3.82 g, 0.040 mol) in THF (20 mL) at −5° C. The reaction mixture was then allowed to warm to room temperature and stirring was continued overnight. The reaction mixture was quenched with water and concentrated in vacuo to give a brown residue which was diluted with ethyl acetate and extracted 1NHCl. The aqueous layers were then combined, made basic (with 1N NaOH) and extracted with ethyl acetate. The organic layers were combined, washed with brine, dried (Na2SO4), filtered and concentrated in vacuo to give a crude residue which was purified by flash column chromatography (1:1 AcOEt/heptane) to give 1-benzyl-4-(2-methoxyethyl)-piperidine-4-carboxylic acid ethyl ester (5.2 g, 84%) as a brown oil. MS (ESI): 306.3 (MH+).

1. stirringstirring
2. waitwas continued for a further 3 hr
3. temperatureto warm to room temperature
4. stirringstirring
5. waitwas continued overnight
6. customThe reaction mixture was quenched with water
7. concentrationconcentrated in vacuo
8. customto give a brown residue which
9. extractionextracted 1NHCl
10. extractionextracted with ethyl acetate
11. washwashed with brine
12. dry with materialdried (Na2SO4)
13. filtrationfiltered
14. concentrationconcentrated in vacuo
15. customto give a crude residue which
16. customwas purified by flash column chromatography (1:1 AcOEt/heptane)