Tetrahydrofuran → Methyl 3-methyl-2-(4-methyl-2-(piperidin-1-yl)-6-p-tolylpyrimidin-5-yl)pentanoate

Temperatur

-15 °C

To a cooled (−15° C.) solution of intermediate 23: methyl 2-(4-methyl-2-(piperidin-1-yl)-6-p-tolylpyrimidin-5-yl)acetate (0.100 g; 0.295 mmol) in dry DMF (1.5 mL) was wadded a 1N solution of LHMDS in THF (0.324 mL; 0.324 mmol) dropwise and the mixture was stirred at (−15° C.) for 15 min, followed by the dropwise addition of 2-iodobutane (0.068 mL; 0.589 mmol). After stirring for 2 h at (−15° C.) the mixture was allowed to warm up to room temperature. After 1 h the reaction was quenched by adding a saturated solution of ammonium chloride and the mixture was extracted twice with ethyl acetate and the combined organic layers were washed with brine, dried over magnesium sulphate, filtered and concentrated under reduced pressure. Purification by flash-chromatography on silica gel using a gradient of ethyl acetate (2-20%) in heptane furnished 0.039 g (33%) of the title compound as a colorless oil.

1. stirringAfter stirring for 2 h at (−15° C.) the mixture
2. temperatureto warm up to room temperature
3. customAfter 1 h the reaction was quenched
4. additionby adding a saturated solution of ammonium chloride
5. extractionthe mixture was extracted twice with ethyl acetate
6. washthe combined organic layers were washed with brine
7. dry with materialdried over magnesium sulphate
8. filtrationfiltered
9. concentrationconcentrated under reduced pressure
10. customPurification by flash-chromatography on silica gel using a gradient of ethyl acetate (2-20%) in heptane

ORD-Eintrag

ord-10b23f9a28724da79540f3ebfec8f2fc

Quelldatensatz

uspto-grants-2014_12

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08906906B2