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

To a precooled (−78° C.) solution of 1.0M sodium bis(trimethylsilyl)amide in THF (13.1 mL, 13.1 mmol) was added dropwise under a nitrogen atmosphere a solution of tert-butyl 4-(3-methoxy-3-oxopropyl)piperidine-1-carboxylate (1.78 g, 6.56 mmol) in 11 mL of THF. After stirring for an additional 25 min, neat iodomethane (1.23 mL, 19.7 mmol) was added dropwise and the reaction mixture was stirred at −78° C. for two more h. The reaction mixture was then poured into 1N HCl solution and the resulting mixture was extracted twice with ether. The combined ethereal layers were washed with brine, dried over anhydrous MgSO4, filtered, and concentrated. Purification by MPLC (silica, 40% ethyl acetate/hexanes) gave tert-butyl 4-(3-methoxy-2-methyl-3-oxopropyl)piperidine-1-carboxylate.

1. stirringthe reaction mixture was stirred at −78° C. for two more h
2. extractionthe resulting mixture was extracted twice with ether
3. washThe combined ethereal layers were washed with brine
4. dry with materialdried over anhydrous MgSO4
5. filtrationfiltered
6. concentrationconcentrated
7. customPurification by MPLC (silica, 40% ethyl acetate/hexanes)

ORD-Eintrag

ord-bb4dd307f2fb44cea03e5c76a819ab79

Quelldatensatz

uspto-grants-2010_04

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07700591B2