Methyl iodide → 1-tert-Butyl 3-ethyl 3-methylpiperidine-1,3-dicarboxylate

A THF (5 mL) solution of 1-tert-butyl 3-ethylpiperidine-1,3-dicarboxylate (1 g, 3.89 mmol) was added dropwise to a THF (15 mL) solution of lithium diisopropylamide (5.83 mmol) in a nitrogen atmosphere at −78 degrees over 5 minutes. The mixture was raised to room temperature, and stirred for 50 minutes. The temperature of the reaction mixture was lowered to −78 degrees again, and methyl iodide (1.21 mL, 19.43 mmol) was added dropwise at −78 degrees over 5 minutes. The reaction mixture was then raised to room temperature, and stirred for 5 hours. After being added to a saturated ammonium chloride aqueous solution, the reaction mixture was stirred for a while, and extracted with diethyl ether. The organic layer was collected, washed once with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The resulting residue was then purified using silica gel column chromatography to obtain the target (698 mg, 66%).

1. customwas lowered to −78 degrees
2. temperatureThe reaction mixture was then raised to room temperature
3. stirringstirred for 5 hours
4. stirringthe reaction mixture was stirred for a while
5. extractionextracted with diethyl ether
6. customThe organic layer was collected
7. washwashed once with saturated brine
8. dry with materialdried over magnesium sulfate
9. concentrationconcentrated under reduced pressure
10. customThe resulting residue was then purified
11. customto obtain the target (698 mg, 66%)

ORD record

ord-d5f4d04f882b452b8bdd4ef5c3808d55

Source dataset

uspto-grants-2013_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08367698B2