Triethylamine → 4-(2-Bromo-3-methyl-phenylcarbamoyl)-piperidine-1-carboxylic acid tert-butyl ester

Piperidine-1,4-dicarboxylic acid mono-tert-butyl ester (5.0 g, 21.80 mmol) was dissolved in dry methylene chloride (32 mL) and dry pyridine (4.50 mL). To the reaction mixture was then added thionyl chloride (3.11 g, 26.17 mmol) under nitrogen atmosphere and the reaction mixture was stirred at room temperature for 30 minutes. To the reaction mixture was then added successively, under nitrogen atmosphere, 2-bromo-3-methyl-phenylamine (as described in J. Org. Chem. 1998, 53, 1170-1176) (4.46 g, 23.99 mmol), dry triethylamine (7.72 g, 76.33 mmol), dry methylene chloride (40 mL), 4-(dimethylamino)pyridine (0.26 g, 2.18 mmol) and the reaction mixture was stirred at room temperature for 24 hours. The reaction mixture was then partitioned with aqueous 2N HCl and tert-butyl methyl ether. The organic layer was washed with aqueous 2N HCl, aqueous NaHCO3, brine, dried with Na2SO4, filtered and the solvent evaporated in vacuo to yield a crude oil. The crude oil was purified via flash chromatography (30% ethyl acetate/hexanes) to yield the title compound as a solid.

1. additionTo the reaction mixture was then added successively, under nitrogen atmosphere
2. customThe reaction mixture was then partitioned with aqueous 2N HCl and tert-butyl methyl ether
3. washThe organic layer was washed with aqueous 2N HCl, aqueous NaHCO3, brine
4. dry with materialdried with Na2SO4
5. filtrationfiltered
6. customthe solvent evaporated in vacuo
7. customto yield a crude oil
8. customThe crude oil was purified via flash chromatography (30% ethyl acetate/hexanes)

ORD-Eintrag

ord-c65f36a0e5ac48d4a7086f62fe039c76

Quelldatensatz

uspto-grants-2010_02

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07655670B2