Lithium borohydride → (5R,6S)-5-(3-chlorophenyl)-6-(5-chloropyridin-2-yl)-1-((S)-1-hydroxybutan-2-yl)piperidin-2-one

Temperature

0 °C

To an ice-cooled solution of 3.95 g (10.0 mmol) of (S)-ethyl 2-((2S,3R)-3-(3-chlorophenyl)-2-(5-chloropyridin-2-yl)-6-oxopiperidin-1-yl)butanoate (Example 121, Step G) in ether (100 mL) was added 486 mg (90%, 20.1 mmol) of lithium borohydride. The resulting light yellow slurry was stirred at 0° C. for 3 h, and then was warmed to room temperature and stirred for an additional 3 h. The reaction was re-cooled to 0° C. and quenched by cautious addition of 1 N HCl until bubbling subsided. The mixture was extracted with EtOAc (3×), and the combined organic layers were washed with saturated aqueous sodium chloride (1×). The organic layer was dried over Na2SO4, filtered and the filtrate was concentrated. Purification of the residue by flash chromatography on silica gel (1 to 7% MeOH/DCM, gradient elution) provided the title compound as a white solid.

1. temperaturewas warmed to room temperature
2. stirringstirred for an additional 3 h
3. temperatureThe reaction was re-cooled to 0° C.
4. customquenched by cautious addition of 1 N HCl
5. customuntil bubbling
6. extractionThe mixture was extracted with EtOAc (3×)
7. washthe combined organic layers were washed with saturated aqueous sodium chloride (1×)
8. dry with materialThe organic layer was dried over Na2SO4
9. filtrationfiltered
10. concentrationthe filtrate was concentrated
11. customPurification of the residue by flash chromatography on silica gel (1 to 7% MeOH/DCM, gradient elution)

ORD record

ord-2e398c6ea15b4524bae3b06139a62c99

Source dataset

uspto-grants-2016_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09296736B2