Reaction #58029

Reaction equation

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

Yield 66.6%

Solvents

dichloromethane

tert-butyl methyl ether

Conditions

Workup

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

Procedure

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.

Source