Diisopropylamine → tert-Butyl 4-formylpiperidine-1-carboxylate

Temperature

-78 °C

To a solution of 15.9 mL of LDA (2 M solution in THF) in 25 mL of THF at −78° C. was added 36.6 mL of diisopropylamine followed by 15.9 ml of (trimethylsilyl)diazomethane dropwise. After stirring at −78° C. for 30 min, 5.25 g of tert-butyl-4oxo-1-piperidinecarboxylate in 10 mL of THF was added slowly over 10 min. The reaction was stirred at −78° C. for 1 hr. After refluxing for 4 hr, the reaction was quenched with cold water and extracted with 3×70 mL of EtOAc. The combined organic phases were dried over MgSO4 and concentrated. The residue was dissolved in 150 mL of EtOAc, then 10 g of silica gel was added. After stirring at rt for 16 hr, silica gel was filtered off. Concentration of filtrate followed by flash chromatography eluting with 25% EtOAc in hexane followed by 100% EtOAc afforded 3.66 g of the title compound as an oil.

1. stirringThe reaction was stirred at −78° C. for 1 hr
2. temperatureAfter refluxing for 4 hr
3. customthe reaction was quenched with cold water
4. extractionextracted with 3×70 mL of EtOAc
5. dry with materialThe combined organic phases were dried over MgSO4
6. concentrationconcentrated
7. dissolutionThe residue was dissolved in 150 mL of EtOAc
8. addition10 g of silica gel was added
9. stirringAfter stirring at rt for 16 hr
10. filtrationsilica gel was filtered off
11. washeluting with 25% EtOAc in hexane

ORD record

ord-6488c4bba0d547c9af7aafdd1ad42cc2

Source dataset

uspto-grants-2001_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06265434B1