Hydrochloric Acid → 2,2-dimethyl-3-(N-Boc-piperidine-4-yl)-propionic acid methyl ester

Temperature

-78 °C

2-methyl-3-(N-Boc-piperidine-4-yl)-propionic acid methyl ester (789 mg, 2.77 mmol) from above was dissolved in dry tetrahydrofuran (2 mL) and cooled to −78° C. To this solution was added lithium diisopropylamide (5.5 mmol, prepared from diisopropylamine and n-butyl lithium). The mixture was stirred at −78° C. for 1 hr and methyl iodide (0.7 mL, 11.24 mmol) was added. The mixture was stirred at −78° C. for 2 hrs until complete consumption of the starting material. The mixture was treated with hydrochloric acid (1N, 10 mL) and extracted with ether. The organic layer was washed with brine and dried over sodium sulfate. After evaporation of the solvents, the residue was purified using flash chromatography (eluting with hexanes and ethyl acetate) to give 2,2-dimethyl-3-(N-Boc-piperidine-4-yl)-propionic acid methyl ester as a colorless oil that slowly turned into a solid (598 mg).

1. stirringThe mixture was stirred at −78° C. for 2 hrs until complete consumption of the starting material
2. extractionextracted with ether
3. washThe organic layer was washed with brine
4. dry with materialdried over sodium sulfate
5. customAfter evaporation of the solvents
6. customthe residue was purified
7. washflash chromatography (eluting with hexanes and ethyl acetate)

ORD record

ord-42bc34b178894d04801226c816237d08

Source dataset

uspto-grants-2012_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08153644B2