Reaktion #58029

Reaktionsgleichung

meldrums acid

4-(2-oxo-ethyl)-piperidine-1-carboxylic acid tert-butyl ester

acetic acid

piperidine

HCl

NaBH4

→

4-[2-(2,2-Dimethyl-4,6-dioxo-[1,3]dioxan-5-yl)-ethyl]-piperidine-1-carboxylic acid tert-butyl ester

Ausbeute 66.6%

Lösungsmittel

dichloromethane

tert-butyl methyl ether

Reaktionsbedingungen

Aufarbeitung

1. 1
   TemperaturThe mixture was heated
2. 2
   Temperaturat reflux for 3 h
3. 3
   Sonstigeto attain room temperature
4. 4
   Waschenthe mixture was washed with NaHCO3 (sat.) and brine
5. 5
   SonstigeThe organic phase was dried
6. 6
   Filtrationfiltered
7. 7
   Einengenconcentrated
8. 8
   workup.DISSOLUTIONThe residue was dissolved in a mixture of EtOH (40 mL) and acetic acid (20 mL)
9. 9
   ExtraktionThe solution was extracted several times with dichloromethane
10. 10
    SonstigeThe combined organic phases were dried
11. 11
    Filtrationfiltered
12. 12
    Einengenconcentrated
13. 13
    Filtrationfiltered through a pad of silica gel (dichloromethane)
14. 14
    SonstigeThe solvent was evaporated

Vorschrift

To a solution of meldrums acid (1.68 g, 11.66 mmol) and 4-(2-oxo-ethyl)-piperidine-1-carboxylic acid tert-butyl ester (2.21 g, 9.72 mmol) in dichloromethane (40 mL) was added acetic acid (0.055 mL, 0.972 mmol) and piperidine (0.096 mL, 0.972 mmol). The mixture was heated at reflux for 3 h, and then allowed to attain room temperature. After being diluted with tert-butyl methyl ether, the mixture was washed with NaHCO3 (sat.) and brine. The organic phase was dried, filtered and concentrated. The residue was dissolved in a mixture of EtOH (40 mL) and acetic acid (20 mL). The solution was cooled to 0° C., and NaBH4 (0.554 g, 14.6 mmol) was added in portions after which the solution was allowed to stir for 30 min at rt and then acidified to pH 3 with 1 M HCl. The solution was extracted several times with dichloromethane. The combined organic phases were dried, filtered, concentrated and filtered through a pad of silica gel (dichloromethane). The solvent was evaporated to give 4-[2-(2,2-Dimethyl-4,6-dioxo-[1,3]dioxan-5-yl)-ethyl]-piperidine-1-carboxylic acid tert-butyl ester as a colorless oil (2.30 g, 65%) which solidified on standing.

Quelle