Sodium hydride → (5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-(cyclopropylmethyl)piperidin-2-one

Temperatur

0 °C

To a solution of 1.5 g (4.7 mmol) of (5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)piperidin-2-one (Example 1, Step E) in 9.4 mL of DMF was added sodium hydride (60% suspension in mineral oil, 244 mg, 6.1 mmol) at 0° C. The reaction was stirred at 0° C. for 20 min and then treated with cyclopropylmethyl bromide (759 μl, 5621 μmol). After being stirred at 25° C. for 5 h, the reaction was quenched (sat. aqueous NH4Cl), extracted (2×EtOAc). The combined organic layers were washed with sat. aq. NaCl and NaHCO3— solutions, dried over Na2SO4, filtered and the filtrate was concentrated under reduced pressure. Purification of the residue by flash chromatography on silica gel (30 to 50% EtOAc/hexanes, gradient elution) provided the title compound as a colorless foam.

1. stirringAfter being stirred at 25° C. for 5 h
2. customthe reaction was quenched (sat. aqueous NH4Cl)
3. extractionextracted (2×EtOAc)
4. washThe combined organic layers were washed with sat. aq. NaCl and NaHCO3— solutions
5. dry with materialdried over Na2SO4
6. filtrationfiltered
7. concentrationthe filtrate was concentrated under reduced pressure
8. customPurification of the residue by flash chromatography on silica gel (30 to 50% EtOAc/hexanes, gradient elution)

ORD-Eintrag

ord-e834bca6a9bb43a28f03dbab4431415a

Quelldatensatz

uspto-grants-2016_03

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09296736B2