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

Temperature

0 °C

To a solution of (3R,5R,6S)-3-allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)piperidin-2-one (Example 42, Step A) (70 mg, 0.19 mmol) in 430 μL of DMF was added sodium hydride (60% suspension in mineral oil, 20 mg, 0.51 mmol) at 0° C. The reaction mixture was stirred at 0° C. for 15 min and after treatment with (bromomethyl)cyclobutane (66 μL, 0.58 mmol) the reaction mixture was heated to 70° C. for 15 h. The reaction mixture was cooled to room temperature, quenched with sat. aqueous NaHCO3 and 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 silica gel prep plate (25% EtOAc/hexanes) provided the title compound as a colorless solid.

1. temperatureThe reaction mixture was cooled to room temperature
2. customquenched with sat. aqueous NaHCO3
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 silica gel prep plate (25% EtOAc/hexanes)

ORD record

ord-581cdfa5db264c97b8219a4fd67af22e

Source dataset

uspto-grants-2013_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08569341B2