Methanol → (5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-hydroxybutan-2-yl)piperidin-2-one

Temperature

0 °C

To an ice-cooled solution of 48.5 g (115 mmol) of (S)-methyl 2-((2S,3R)-3-(3-chlorophenyl)-2-(4-chlorophenyl)-6-oxopiperidin-1-yl)butanoate (Example 185, Step A) in ethyl ether (850 mL) was added 5.96 g (90%, 246 mmol) of lithium borohydride. The resulting light yellow solution was stirred at 0° C. for 3 h, and then MeOH (2.5 mL) and more ethyl ether (100 mL) were added. Gas evolution was observed upon the addition of MeOH. After 40 min, the reaction was quenched by cautious addition of 1 N HCl until bubbling subsided. The mixture was extracted with EtOAc (2×), 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 to afford the title compound as a white foam. The crude product was used directly in the next step without further purification.

1. waitAfter 40 min
2. customthe reaction was quenched by cautious addition of 1 N HCl
3. customuntil bubbling
4. extractionThe mixture was extracted with EtOAc (2×)
5. washthe combined organic layers were washed with saturated aqueous sodium chloride (1×)
6. dry with materialThe organic layer was dried over Na2SO4
7. filtrationfiltered
8. concentrationthe filtrate was concentrated

ORD record

ord-1a307a8b6ad74600b83f885114d4d240

Source dataset

uspto-grants-2013_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08569341B2