反应详情

Sodium hydride (5.0 g of 50% dispersion in mineral oil) was added portionwise to a stirred solution of 4-hydroxy-1-methyl-piperidine (11.5 g) in dry dimethylformamide (80 ml). The mixture was stirred at room temperature for 1 hour and then cooled to 10° C. A solution of ethyl 4-chloroacetoacetate (8.2 g) in dry dimethylformamide (20 ml) was added dropwise with stirring and stirring was continued for a further 20 hours at room temperature. Ethanol (10 ml) was added and the solution was evaporated to dryness. The residue was partitioned between dichloromethane and dilute hydrochloric acid. The organic layer was separated, dried over sodium sulphate and evaporated to given an oil which was partitioned between acetonitrile and petrol to remove mineral oil. The acetonitrile extract was evaporated to give the title compound as an oil (10.3 g) which was used without further purification.

1. temperaturecooled to 10° C
2. stirringwith stirring
3. stirringstirring
4. waitwas continued for a further 20 hours at room temperature
5. customthe solution was evaporated to dryness
6. customThe residue was partitioned between dichloromethane and dilute hydrochloric acid
7. customThe organic layer was separated
8. dry with materialdried over sodium sulphate
9. customevaporated
10. customwas partitioned between acetonitrile and petrol
11. customto remove mineral oil
12. extractionThe acetonitrile extract
13. customwas evaporated