Ethyl Acetate → 2-((3R,5R,6S)-5-(3-Chlorophenyl)-6-(4-chlorophenyl)-3-methyl-2-oxo-1-((S)-2-oxopentan-3-yl)piperidin-3-yl)acetic acid

Ruthenium(III) chloride hydrate (1.404 g, 6.23 mmol) was added to a solution of (3S,5R,6S)-3-allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((3S)-2-hydroxypentan-3-yl)-3-methylpiperidin-2-one (Example 151, Step C) (130.30 g, 283 mmol) and NaIO4 (61.5 g) in EtOAc (630 mL), CH3CN (630 mL) and water (935 mL) at 18° C. The remaining NaIO4 (307.5 g) was added in five portions over 2.5 hours while maintaining the temperature below 26° C. 15 minutes after the final addition of NaIO4 the cooling bath was removed and the reaction mixture was stirred at ambient temperature for 50 minutes. The tan reaction mixture was filtered using a Büchner funnel and washed with EtOAc (500 mL) and CH3CN (500 mL). The layers were separated and the aqueous layer was extracted with EtOAc twice. The organics were pooled, washed with 10% aq. NaHSO3 (3×1 L), brine (1 L), dried (Na2SO4), decanted and concentrated in vacuo to provide a green oil. The material was dissolved in a minimum amount of DCM and purified using two 1.5 kg Biotage® Snap™ columns (Biotage, LLC, Charlotte, N.C.) and eluting with 10-50% (15% MeOH/acetone)/hexanes to provide a light pink foam (109.67 g).

1. temperaturewhile maintaining the temperature below 26° C
2. customwas removed
3. customThe tan reaction mixture
4. filtrationwas filtered
5. washwashed with EtOAc (500 mL) and CH3CN (500 mL)
6. customThe layers were separated
7. extractionthe aqueous layer was extracted with EtOAc twice
8. washwashed with 10% aq. NaHSO3 (3×1 L), brine (1 L)
9. dry with materialdried (Na2SO4)
10. customdecanted
11. concentrationconcentrated in vacuo
12. customto provide a green oil
13. custompurified
14. washeluting with 10-50% (15% MeOH/acetone)/hexanes

ORD record

ord-1508a330ed054193bcf8b2f54b366031

Source dataset

uspto-grants-2016_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09296736B2